TW202317523A - Biomarkers for colorectal cancer treatment - Google Patents

Biomarkers for colorectal cancer treatment Download PDF

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TW202317523A
TW202317523A TW111126187A TW111126187A TW202317523A TW 202317523 A TW202317523 A TW 202317523A TW 111126187 A TW111126187 A TW 111126187A TW 111126187 A TW111126187 A TW 111126187A TW 202317523 A TW202317523 A TW 202317523A
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abnormalities
drug sensitivity
individual
drug resistance
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袁鵬飛
金鳴
張永建
申紅豔
楊玲
劉娜
蘇美華
鄭雅茹
李玉蘭
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大陸商北京輯因醫療科技有限公司
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Abstract

The present disclosure provides biomarkers associated with sensitivity or resistance of colorectal cancer in an individual to treatment with a DNA damaging agent, as well as methods, kits and reagents for detecting such biomarkers. The disclosure also provides methods for evaluating, identifying, assessing, and/or treating an individual having a colorectal cancer.

Description

結直腸癌治療的生物標記Biomarkers for Colorectal Cancer Therapy

本申請要求2021年7月12日提交的國際專利申請號PCT/CN2021/105822和2021年7月12日提交的國際專利申請號PCT/CN2021/105816的優先權，其各自內容藉由引用以其整體併入本文。This application claims priority to International Patent Application No. PCT/CN2021/105822 filed on July 12, 2021 and International Patent Application No. PCT/CN2021/105816 filed on July 12, 2021, the contents of each of which are hereby incorporated by reference Incorporated into this article as a whole.

本申請涉及與結直腸癌相關的生物標記，以及結直腸癌的診斷、評估和治療方法。The present application relates to biomarkers associated with colorectal cancer, and methods for diagnosis, evaluation and treatment of colorectal cancer.

結直腸癌是世界上第三常見的癌症，第二大癌症相關死亡原因，也是導致胃腸道癌死亡的主要原因。按照傳統的病理分期，結直腸癌根據腫瘤浸潤、淋巴結轉移和遠端轉移的深度分為0期、Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期。目前，早期結直腸癌的治療通常採用手術或放療。除了手術和放療外，中晚期患者通常會結合化療和靶向藥物治療進行系統治療。在目前的治療下，早期結直腸癌的五年生存率超過90%，而晚期轉移性結直腸癌的五年生存率僅為14%。Colorectal cancer is the third most common cancer in the world, the second leading cause of cancer-related death, and the leading cause of death from gastrointestinal cancer. According to the traditional pathological staging, colorectal cancer is divided into stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ and stage Ⅳ according to the depth of tumor infiltration, lymph node metastasis and distant metastasis. Currently, early-stage colorectal cancer is usually treated with surgery or radiation. In addition to surgery and radiotherapy, patients with advanced disease usually receive systemic treatment in combination with chemotherapy and targeted drug therapy. With current treatments, the five-year survival rate for early-stage colorectal cancer is more than 90%, compared with only 14% for advanced metastatic colorectal cancer.

一些抗癌療法，例如放射療法和某些化療藥物，可能會導致雙鏈DNA斷裂(DSB)。同源重組(HR)和非同源末端連接(NHEJ)是修復真核細胞中DSB的兩種主要路徑。HR藉由複製一段同源DNA來修復DSB，而NHEJ藉由處理和重新連接DSB末端來修復DSB (Thompson、et al.、2001; Lieber、et al.、2004)。與具有高保真DNA修復的HR不同，NHEJ往往容易出錯，因為重新連接前DSB位點的小缺失或廣泛降解，通常會引入大規模基因組重組，導致遺傳不穩定和細胞死亡。Some anticancer treatments, such as radiation therapy and certain chemotherapy drugs, can cause double-strand DNA breaks (DSBs). Homologous recombination (HR) and non-homologous end joining (NHEJ) are two major pathways for repairing DSBs in eukaryotic cells. HR repairs DSBs by duplicating a stretch of homologous DNA, whereas NHEJ repairs DSBs by manipulating and rejoining DSB ends (Thompson, et al., 2001; Lieber, et al., 2004). Unlike HR with high-fidelity DNA repair, NHEJ is often error-prone because small deletions or extensive degradation of DSB sites prior to reconnection often introduce large-scale genome recombination, leading to genetic instability and cell death.

聚(ADP核醣)聚合酶(PARP)與結直腸癌有關。PAPR蛋白與DNA位點結合並催化蛋白質受質上多聚ADP核醣鏈的合成。藉由這種催化作用，PARP1可以將其他DNA修復蛋白募集到損傷部位，共同修復DNA損傷。PARP抑制劑(PARPi)與PARP催化位點結合，導致PARP蛋白未能從DNA損傷位點脫落，導致DNA複製叉停滯，無法修復DSB。PARP抑制劑藉由抑制腫瘤細胞DNA損傷修復，促進腫瘤細胞凋亡，最終達到治療效果。儘管已開發出多種PARP抑制劑作為潛在的抗癌藥物，這些抑制劑的有效性仍有待提高。Poly(ADP-ribose) polymerase (PARP) has been implicated in colorectal cancer. PAPR proteins bind to DNA sites and catalyze the synthesis of poly-ADP-ribose chains on protein substrates. Through this catalysis, PARP1 can recruit other DNA repair proteins to the damage site to work together to repair DNA damage. PARP inhibitor (PARPi) binds to the PARP catalytic site, resulting in the failure of PARP protein to shed from the site of DNA damage, leading to stalled DNA replication forks and failure to repair DSBs. PARP inhibitors promote the apoptosis of tumor cells by inhibiting the DNA damage repair of tumor cells, and finally achieve the therapeutic effect. Although a variety of PARP inhibitors have been developed as potential anticancer drugs, the effectiveness of these inhibitors remains to be improved.

毛細血管擴張性共濟失調突變(Ataxia telangiectasia mutated)和Rad3相關的(ATR)激酶是絲氨酸/蘇氨酸蛋白激酶的磷脂醯肌醇3-激酶相關激酶(PIKK)家族的成員。ATR激酶是DNA損傷反應的主要調節劑，並被廣泛存在的單鏈DNA結構(ssDNA)啟動。大多數ssDNA源於停滯的DNA複製壓力或其他類型的DNA損傷，包括切除的DNA DSB、交聯、鹼基加合物和DNA聚合酶的抑制。當DNA損傷發生時，ATR主要藉由其下游標靶CHK1的磷酸化和啟動來發揮作用，從而導致停滯的複製叉穩定、起始激勵、DNA損傷修復和細胞週期各種檢查點的啟動。儘管對ATR及其作為抗癌標靶的巨大潛力已有數十年的瞭解，ATR抑制劑(ATRi)在癌症治療中尚未取得臨床成功(F.M. Barnieh et al. “Progress towards a clinically-successful ATR inhibitor for cancer therapy.” Current Research in Pharmacology 和 Drug Discovery、2021; Volume 2、100017)。 Ataxia telangiectasia mutated and Rad3-related (ATR) kinases are members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family of serine/threonine protein kinases. ATR kinase is a master regulator of the DNA damage response and is initiated by ubiquitous single-stranded DNA structures (ssDNA). Most ssDNA originates from stalled DNA replication stress or other types of DNA damage, including excised DNA DSBs, crosslinks, base adducts, and inhibition of DNA polymerases. When DNA damage occurs, ATR mainly functions through the phosphorylation and initiation of its downstream target CHK1, leading to the stabilization of stalled replication forks, initiation stimulation, DNA damage repair and initiation of various checkpoints in the cell cycle. Despite decades of understanding of ATR and its enormous potential as an anticancer target, ATR inhibitors (ATRi) have not yet achieved clinical success in cancer therapy (FM Barnieh et al. “Progress towards a clinically-successful ATR inhibitor for cancer therapy." Current Research in Pharmacology and Drug Discovery , 2021; Volume 2, 100017).

本申請在一態樣提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中選擇所述個體進行治療的依據是，來自所述個體的樣本在一個或多個選自下組的藥物敏感性基因中具有一種或多種藥物敏感性異常（例如藥物敏感性突變）PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中選擇所述個體進行治療的依據是來自所述個體的樣本中具有高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分；其中所述藥物敏感性異常(例如突變)是一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B；並且其中耐藥異常(例如突變)是一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。The present application provides in one aspect a method of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is selected for treatment Based on the fact that the sample from said individual has one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1 , FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2 , RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT , NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2 , CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1 , PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1 , NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D , GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2 A. BCL2L1 , MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4 , FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6 , MSH2, MLH1, and HLA-B. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human) comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is selected for treatment is based on a composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) in samples from the individual above a threshold level; wherein the drug sensitivity abnormalities (e.g., mutation) is one or more drug sensitivity abnormalities (e.g. mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP , RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B and wherein the drug resistance abnormality (such as a mutation) is one or more drug resistance abnormalities (such as a mutation) in one or more drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B , BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，提供了一種治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中選擇所述個體進行治療的依據是來自所述個體的樣本中具有高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分；其中所述藥物敏感性異常(例如突變)是一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B；並且其中所述耐藥異常(例如突變)是一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, there is provided a method of treating colorectal cancer in an individual (e.g., a human) comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is selected for treatment is based on a composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) in samples from the individual above a threshold level; wherein the drug sensitivity abnormalities (e.g., mutation) is one or more drug sensitivity abnormalities (e.g. mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP , RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B and wherein the drug resistance abnormality (such as a mutation) is one or more drug resistance abnormalities (such as a mutation) in one or more drug resistance genes selected from the group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中選擇所述個體進行治療的依據是，來自所述個體的樣本在一個或多個選自下組的藥物敏感性基因中具有一種或多種藥物敏感性異常（例如藥物敏感性突變）GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中選擇所述個體進行治療的依據是來自所述個體的樣本中具有高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分；其中所述藥物敏感性異常(例如突變)是一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM；並且其中所述耐藥異常(例如突變)是一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is selected for treatment Based on that the sample from said individual has one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B , ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human) comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is selected for treatment is based on a composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) in samples from the individual above a threshold level; wherein the drug sensitivity abnormalities (e.g., mutation) is one or more drug sensitivity abnormalities (e.g. mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM; mutation) is one or more drug resistance abnormalities (such as mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中選擇所述個體進行治療的依據是，來自所述個體的樣本在一個或多個選自下組的藥物敏感性基因中具有一種或多種藥物敏感性異常（例如藥物敏感性突變）PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中選擇所述個體進行治療的依據是其在一個或多個選自下組的藥物敏感性基因中具有一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中選擇所述個體進行治療的依據是來自所述個體的樣本中具有高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分；其中所述藥物敏感性異常(例如突變)是一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1；並且其中所述耐藥異常(例如突變)是一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中選擇所述個體進行治療的依據是來自所述個體的樣本中具有高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分；其中所述藥物敏感性異常(例如突變)是一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX；並且其中所述耐藥異常(例如突變)是一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment based on, The individual's sample has one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM , UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR , MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1 , CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1 , RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51 D. , PMS2, MSH6, MSH2, MLH1, and STAP1. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment on the basis that he or she is in a One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN , RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2 , SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment based on the A composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) in a sample from an individual above a threshold level; wherein the drug sensitivity abnormalities (e.g., mutations) are one or more One or more drug sensitivity abnormalities (e.g. mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1 and wherein the drug resistance abnormality (such as a mutation) is one or more drug resistance abnormalities (such as a mutation) in one or more drug resistance genes selected from the group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment based on the A composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) in a sample from an individual above a threshold level; wherein the drug sensitivity abnormalities (e.g., mutations) are one or more One or more drug sensitivity abnormalities (e.g. mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX; and wherein the drug resistance abnormality (such as a mutation) is one or more drug resistance abnormalities in one or more drug resistance genes selected from the group below ( e.g. mutations): PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的ATRi，其中選擇所述個體進行治療的依據是來自所述個體的樣本在一個或多個選自下組的藥物敏感性基因中具有一種或多種藥物敏感性異常(例如藥物敏感性突變)： ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的ATRi，其中選擇所述個體進行治療的依據是來自所述個體的樣本中具有高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分；其中所述藥物敏感性異常(例如突變)是一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B；並且其中所述耐藥異常(例如突變)是一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of ATRi, wherein the individual is selected for treatment based on samples with one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC , ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4 , SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5 , STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, AN APC7 , DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4 A3 , PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4 , FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human) comprising administering to the individual an effective amount of ATRi, wherein the individual is selected for treatment based on A composite score of drug susceptibility abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) in a sample above a threshold level; wherein the drug susceptibility abnormalities (e.g., mutations) are one or more selected One or more drug sensitivity abnormalities (e.g. mutations) in drug sensitivity genes from the following group: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO 1. TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B; and wherein the drug resistance abnormality (eg mutation) is one or more drug resistance selected from the group One or more resistance abnormalities (eg, mutations) in genes: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK 2. EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含從來自所述個體的樣本中獲知一個或多個選自下組的藥物敏感基因中的一種或多種藥物敏感性異常（例如藥物敏感性突變）：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，並且回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體的樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising learning from a sample from said individual one or more of one or more drug-sensitive genes selected from the group consisting of Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and in response to said learning, administering to said individual an effective amount of DNA Injuring agents (eg PARPi or ATRi). In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more of the drug sensitivity genes selected from the group consisting of one or more of the samples from the individual or multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, Z NF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance genes selected from the group below One or more resistance abnormalities (eg, resistance mutations): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8 , PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2 , FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR , XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B , EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR 1 , TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5 , CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4 , POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2 , DBF4 , CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2 , and GAB1, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體的樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並回應所述獲知，給予所述個體有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance genes selected from the group below or multiple resistance abnormalities (such as resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi ). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，以及來自所述個體樣本中的一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1 , GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human) comprising knowing one or more drug sensitivity aberrations in one or more drug sensitivity genes selected from the group consisting of (e.g., drug susceptibility mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual samples ): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含從來自所述個體的樣本中獲知一個或多個選自下組的藥物敏感基因中的一種或多種藥物敏感性異常（例如藥物敏感性突變）PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，以及回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：來自所述個體樣本的ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，並且回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1以及來自所述個體樣本中的一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，並回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1並且回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising learning from a sample from said individual one or more of one or more drug-sensitive genes selected from the group consisting of Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations) PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and in response to said learning, administering to said individual Give an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human) comprising knowing one or more drug sensitivity aberrations in one or more drug sensitivity genes selected from the group consisting of (e.g., drug susceptibility mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and in response to said learning, administering to said individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human) comprising knowing one or more drug sensitivity aberrations in one or more drug sensitivity genes selected from the group consisting of (e.g., drug susceptibility mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1 and one or more resistance selected from the following group in the individual sample One or more resistance abnormalities (eg, resistance mutations) in drug genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1 , LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN , PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1 , EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5 , BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, and in response to said learning, administering to said individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C , RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4 , NIPBL, and ATRX and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2 , GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1 , CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1 and responsive to said learning, administering to said individual an effective amount of a PARP inhibitor. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含從來自所述個體的樣本中獲知一個或多個選自下組的藥物敏感基因中的一種或多種藥物敏感性異常（例如藥物敏感性突變）：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，並回應所述獲知，向所述個體投予有效量的ATRi。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，並回應所述獲知，向所述個體投予有效量的ATRi。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising learning from a sample from said individual one or more of one or more drug-sensitive genes selected from the group consisting of Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A , TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2 , RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D , GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP , MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN 1A, SMAD7 , ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28 , LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and responsive to said learning, administering to said individual an effective amount of ATRi. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A , TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2 , RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D , GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP , MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN 1A, SMAD7 , ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28 , LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, and responsive to said learning, administering to said individual an effective amount of ATRi. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，並回應所述獲知向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and in response to said learning administering to said individual an effective amount of DNA damage agent (such as PARPi or ATRi). In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance genes selected from the group below or multiple resistance abnormalities (such as resistance mutations): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, Plec, Crebbp, RELA, E2F3, ITIH6, BRPF3, Anapc7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MyH14, RASL10B, MyH9, FGF19, TNFRSF17, CUL9, CD C25A, KMT2D, Foxg1, Arid1a, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DB F4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance genes selected from the group below or multiple resistance abnormalities (such as resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi). In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1 , GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1 , GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group : RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN , VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，並回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，並回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，並回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，並回應所述獲知，向所述個體投予有效量的PARP抑制劑。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and in response to said learning, to said individual An effective amount of a PARP inhibitor is administered. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C , RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4 , NIPBL, and ATRX, and in response to said learning, administering to said individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and one or more selected from the following group One or more resistance abnormalities (eg, resistance mutations) in resistance genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19 , and in response to said learning, administering to said individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more of a drug sensitivity gene selected from a sample from said individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2 , GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1 , CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, and in response to said learning, administering to said individual an effective amount of a PARP inhibitor. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，並回應所述獲知，向所述個體投予有效量的ATR抑制劑。在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，並回應所述獲知，向所述個體投予有效量的ATR抑制劑。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more of a drug sensitivity gene selected from a sample from said individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A , SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and responsive to said learning, administering to said individual an effective amount of an ATR inhibitor. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising knowing one or more drug sensitivity genes selected from the group consisting of one or more of the drug sensitivity genes in a sample from the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A , TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2 , RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D , GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP , MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN 1A, SMAD7 , ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28 , LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, and responsive to said learning, administering to said individual an effective amount of an ATR inhibitor. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，包含偵測所述樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, HPRT1, DNAH11, DPM2, DPM2, DPM2 , PTPN11, Wnt7b, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, One or more drug resistance abnormalities (such as drug resistance mutations) in RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2 , MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL , GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2 , DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B , E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA , HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS1 3C , PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2 , PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1 Dock1, Znf469, PLA2G12B, EGFR, WDFY4, USP9X, Gal3st4, Kiaa1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6,, Dock6,, Dock6, Dock6, ROCK2, Comp, Arid2, RHOA, JPH3, TFDP1 , FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, comprising detecting one or more of said samples selected from the following One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in the drug sensitivity genes of the group: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B , SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1 , NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1 , DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP , SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF , LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2 , CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2 , HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB 1 , TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1 , USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more One or more drug resistance abnormalities (such as drug resistance mutations) in a drug resistance gene selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, C BFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1.

在一些實施方案中，獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，包含偵測所述樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, HPRT1, DNAH11, DPM2, DPM2, DPM2 , PTPN11, Wnt7b, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, One or more drug resistance abnormalities (such as drug resistance mutations) in RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1 , MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR , SRC, PIK3CA, CHD2, PARP1, and EIF4B, comprising detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN , CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220 , CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5 , KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1 , ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1 , POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4 , SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D , ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1 , CDC42 , DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT 7B , OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1 , RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B.

在一些實施方案中，獲知來自所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，包含偵測所述樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1 , RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, comprising detection of one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B in the sample , ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, And/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B.

在一些實施方案中，獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，包含偵測所述樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，包含偵測所述樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, One or more drug resistance abnormalities (such as drug resistance mutations) in EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more drug resistance genes selected from the group consisting of: PARP1 , MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN , EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1 , YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1 , AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3 , ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, comprising detecting one or more drug-sensitive drugs selected from the following group in the sample Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2 , GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS , RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6 , RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2 A One or more drug resistance abnormalities (such as drug resistance mutations) in multiple drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or one or more drug resistance genes selected from the group below One or more resistance abnormalities (such as resistance mutations) in: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1 , EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1 , HSP90B1, CCNA1, and RBL1, comprising detecting one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6 in the sample , BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2 , CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or one or more selected from the following group One or more resistance abnormalities (such as resistance mutations) in resistance genes: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1.

在一些實施方案中，獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，包含偵測所述樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A , POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or One or more drug resistance abnormalities (eg, drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1 , SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB , PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L , CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1 , E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF 4G2 , DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, comprising detecting one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group in the sample: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ , HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、 BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or one or One or more drug resistance abnormalities (such as drug resistance mutations) in multiple drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2 , CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1 , DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1 , DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1 , ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DB F4 , CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含偵測所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，並向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising detecting one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of the individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF56 8. FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes selected from the following group One or more resistance abnormalities (eg, resistance mutations): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8 , PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2 , FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR , XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B , EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR 1 , TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5 , CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4 , POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2 , DBF4 , CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2 , and GAB1, and administering to the individual an effective amount of a DNA damaging agent (eg, PARPi or ATRi).

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含偵測所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並且向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising detecting one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of the individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF56 8. FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes selected from the following group One or more resistance abnormalities (eg, resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3 , MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and an effective amount of a DNA damaging agent (eg, PARPi or ATRi) is administered to the individual.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含偵測所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並且向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising detecting one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of the individual Abnormal drug sensitivity (e.g., drug-sensitive mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or one or more drug resistance abnormalities (such as drug resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12 , PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and an effective amount of a DNA damaging agent (eg, PARPi or ATRi) is administered to the individual.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含偵測所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，並向所述個體投予有效量的PARP抑制劑。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含偵測所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，並向所述個體投予有效量的PARP抑制劑。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising detecting one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of the individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more selected from the group One or more resistance abnormalities (such as resistance mutations) in the resistance genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1 , EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R , NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1 , GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1 , EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, and an effective amount of a PARP inhibitor is administered to the individual. In some embodiments, provided herein are methods of treating colorectal cancer in an individual (e.g., a human), comprising detecting one or more drugs in one or more drug sensitivity genes selected from the group consisting of in a sample of the individual Sensitivity abnormalities (eg, drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D , PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL , and ATRX, and/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, and administering to the individual an effective amount of a PARP inhibitor.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含偵測所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，並向所述個體投予有效量的ATR抑制劑。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising detecting one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of the individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A , SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, One or more drug resistance abnormalities (such as drug resistance mutations) in LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or one or more drug resistance genes selected from the group: RHEB, MED12 , PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6 , TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML , PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2 , NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X , GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4 , MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, and administering an effective amount of an ATR inhibitor to the individual.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B。在一些實施方案中，本文提供治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1, 並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is in a One or more drug sensitivity abnormalities (such as drug sensitivity mutations) are contained in one or more drug sensitivity genes selected from the group: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA , DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1 , SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA , RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3 , ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1 , EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3 , TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, R PS6KA5 , BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, G RB2 , CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1 , FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B. In some embodiments, provided herein are methods of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is in one or more One or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) are contained in a drug sensitivity gene selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4 , CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4 , NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1 , FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1 , ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300 , KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1 , RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5 , BMP8B , MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR 1 , FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP A One or more drug resistance abnormalities (such as drug resistance mutations) in multiple drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, Foxg1, Arid1a, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, VPS13C, PLA2G6, PPP2R1B, BMP7, S Trada, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, M APK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, and the combined score of abnormal drug sensitivity (such as drug sensitivity mutation) and drug resistance abnormality (such as drug resistance mutation) is higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B, 並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is in one or One or more drug sensitivity abnormalities (such as drug sensitivity mutations) are contained in a plurality of drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6 KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB 2. CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and One or more resistance abnormalities (eg, resistance mutations) in one or more resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R , RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and drug sensitivity abnormalities (such as drug susceptibility mutations) and drug resistance abnormalities (such as drug resistance mutations) were above the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM。在一些實施方案中，本文提供治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARPi或ATRi)，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is in a One or more drug sensitivity abnormalities (such as drug sensitivity mutations) are contained in one or more drug sensitivity genes selected from the group: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ , GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM. In some embodiments, provided herein are methods of treating colorectal cancer in an individual (e.g., a human), comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi), wherein the individual is in one or more One or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) are contained in a drug sensitivity gene selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B , DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and one or more drug resistance selected from the group One or more resistance abnormalities (eg, resistance mutations) in genes: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, and in which drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (e.g. drug resistance mutations) with a composite score above the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的PARP抑制劑，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1, 並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual has one or more selected from the group consisting of Drug sensitivity genes containing one or more drug sensitivity abnormalities (such as drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual has one or more selected from the group consisting of Drug sensitivity genes contain one or more drug sensitivity abnormalities (such as drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual has one or more selected from the group consisting of Drug sensitivity genes containing one or more drug sensitivity abnormalities (such as drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and One or more resistance abnormalities (eg, resistance mutations) in one or more resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB , CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN , PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2 , DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4 , RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A , CHEK1, PKMYT1, SIDT2, and FGF19, and the combined score of drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) is higher than the threshold level. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual has one or more selected from the group consisting of Drug sensitivity genes contain one or more drug sensitivity abnormalities (such as drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC , RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2 , PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, and drug sensitivity abnormalities (such as drug sensitivity mutations) and The composite score of drug resistance abnormalities (such as drug resistance mutations) is higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的ATR抑制劑，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B。在一些實施方案中，本文提供了治療個體(例如人)中的結直腸癌的方法，包含向所述個體投予有效量的ATR抑制劑，其中所述個體在一個或多個選自下組的藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of an ATR inhibitor, wherein the individual is selected from one or more of One or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in the group of drug sensitivity genes: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL , EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1 , MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D , ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1 , LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FO XO1 , TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1 , FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B. In some embodiments, provided herein is a method of treating colorectal cancer in an individual (eg, a human), comprising administering to the individual an effective amount of an ATR inhibitor, wherein the individual has one or more selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in the drug sensitivity genes: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO 1. TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more drug resistance abnormalities in one or more drug resistance genes selected from the group below (eg Drug resistance mutations): RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1 , APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC , MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3 , AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469 , PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3 , ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, and drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as resistance drug mutation) was higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種鑒定可獲益於包含投予DNA損傷劑(例如PARPi或ATRi)的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B, 其中，在所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在，表明所述個體是可從所述治療中獲益的個體。在一些實施方案中，本文提供了鑒定不可獲益於包含投予DNA損傷劑(例如PARPi或ATRi)的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1, 其中，在所述樣本中一種或多種耐藥性異常（例如耐藥突變）的存在，表明所述個體是不可從所述治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予DNA損傷劑(例如PARPi或ATRi)的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1, 其中當藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準時，將所述個體鑒定為可從治療中獲益的個體。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) comprising a One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, wherein the presence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in the sample indicates that the individual is one who would benefit from the treatment. In some embodiments, provided herein are methods of identifying individuals (e.g., humans) with colorectal cancer who would not benefit from treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) comprising a One or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group are detected in samples of the individual: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, wherein the presence of one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample indicates that the Said individual is an individual who will not benefit from said treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) comprising a One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more resistance abnormalities (eg, resistance mutations) in one or more resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53 , CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2 , MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12 , YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1 , KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1 , MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R 1B, BMP7 , STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2 PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, Chuk, Dok4, POLRMT, PLCE1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CC NE1, Dock1, Znf469, PLA2G12B, EGFR , WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B , FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, where abnormal drug sensitivity (such as drug sensitivity mutation) and drug resistance abnormality (such as drug resistance mutation ) above a threshold level, the individual is identified as an individual who may benefit from treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種鑒定可獲益於包含投予DNA損傷劑(例如PARPi或ATRi)的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B, 其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準時，將所述個體鑒定為可從治療中獲益的個體。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) comprising a One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (eg, drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4 , CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1 , and EIF4B, wherein when the combined score of drug sensitivity abnormality (eg, drug sensitivity mutation) and drug resistance abnormality (eg, drug resistance mutation) is above a threshold level, the individual is identified as an individual who may benefit from treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種鑒定可獲益於包含投予DNA損傷劑(例如PARPi或ATRi)的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM, 其中所述樣本中存在一種或多種藥物敏感性異常(例如藥物敏感性突變)時將所述個體鑒定為可獲益於治療的個體。在一些實施方案中，本文提供了鑒定不可獲益於包含投予DNA損傷劑(例如PARPi或ATRi)的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中所述樣本中存在一種或多種耐藥異常(例如耐藥突變)時將所述個體鑒定為不可從治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予DNA損傷劑(例如PARPi或ATRi)的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準時，將所述個體鑒定為可從治療中獲益的個體。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) comprising a One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, where The presence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in the sample identifies the individual as one who would benefit from treatment. In some embodiments, provided herein are methods of identifying individuals (e.g., humans) with colorectal cancer who would not benefit from treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) comprising a One or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group are detected in samples of the individual: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B , wherein the presence of one or more drug resistance abnormalities (eg, drug resistance mutations) in the sample identifies the individual as not benefiting from treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) comprising a One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and One or more resistance abnormalities (eg, resistance mutations) in one or more resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R , RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, among which the drug sensitivity was abnormal ( When the combined score of drug-sensitivity mutations) and drug-resistance abnormalities (eg, drug-resistance mutations) is above a threshold level, the individual is identified as an individual who may benefit from treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種鑒定可獲益於包含投予PARP抑制劑的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1, 其中，在所述樣本中一種或多種藥物敏感性異常（例如藥物敏感性突變）的存在，表明所述個體是可從所述治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予PARP抑制劑的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX, 其中，在所述樣本中一種或多種藥物敏感性異常（例如藥物敏感性突變）的存在，表明所述個體是可從所述治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予PARP抑制劑的治療的患有結直腸癌的個體（例如人）的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19, 其中，在所述樣本中一種或多種耐藥性異常（例如耐藥突變）的存在，表明所述個體是不可從所述治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予PARP抑制劑的治療的患有結直腸癌的個體（例如人）的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中，在所述樣本中一種或多種耐藥性異常（例如耐藥突變）的存在，表明所述個體是不可從所述治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予PARP抑制劑的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19, 其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準時，將所述個體鑒定為可從治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予PARP抑制劑的治療的患有結直腸癌的個體(例如人)的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準時，將所述個體鑒定為可從治療中獲益的個體。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of a PARP inhibitor, the method comprising a sample from the individual Detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2 , MSH6, MSH2, MLH1, and STAP1, wherein the presence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in the sample indicates that the individual is one who may benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of a PARP inhibitor, the method comprising a sample from the individual Detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, wherein the presence of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in the sample indicates The individual is one who would benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of a PARP inhibitor, the method comprising a sample from the individual Detecting one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL , RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B , PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1 , EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C , MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras , CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, wherein the presence of one or more drug resistance abnormalities (eg, drug resistance mutations) in the sample indicates that the individual is not an individual who will not benefit from the treatment . In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of a PARP inhibitor, the method comprising a sample from the individual Detecting one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras , TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B , CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, wherein the presence of one or more drug resistance abnormalities (eg, drug resistance mutations) in the sample indicates that the individual is Individuals who will not benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of a PARP inhibitor, the method comprising a sample from the individual Detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2 , MSH6, MSH2, MLH1, and STAP1, and one or more resistance abnormalities (eg, resistance mutations) in one or more resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53 , CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2 , MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12 , YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1 , KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1 , MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, where the combined score of drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) is higher than the threshold level , identifying the individual as an individual who would benefit from treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of a PARP inhibitor, the method comprising a sample from the individual Detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance abnormalities (such as drug resistance mutations): PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2 , RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, among which drug sensitivity When the combined score of abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) is above a threshold level, the individual is identified as an individual who may benefit from treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了鑒定可獲益於包含投予ATR抑制劑的治療的患有結直腸癌的個體（例如人）的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，其中，在所述樣本中一種或多種藥物敏感性異常（例如藥物敏感性突變）的存在，表明所述個體是可從所述治療中獲益的個體。在一些實施方案中，本文提供了一種鑒定可獲益於包含投予ATR抑制劑的治療的患有結直腸癌的個體（例如人）的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中，在所述樣本中一種或多種耐藥性異常（例如耐藥突變）的存在，表明所述個體是不可從所述治療中獲益的個體。在一些實施方案中，本文提供了鑒定可獲益於包含投予ATR抑制劑的治療的患有結直腸癌的個體（例如人）的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1, 其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準時，將所述個體鑒定為可從治療中獲益的個體。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of an ATR inhibitor, the method comprising detecting in a sample from the individual Detect one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1 , PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30 , PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11 , NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DI DO1 , CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PA RP14 , AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2 , CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, wherein one or more drug sensitivity is abnormal in said sample (e.g. drug sensitivity mutations), indicating that the individual is one who would benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of an ATR inhibitor, the method comprising a sample from the individual Detecting one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1 , TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2 , FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B , DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT , PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH 9 , EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2 , and GAB1, wherein the presence of one or more drug resistance abnormalities (eg, drug resistance mutations) in said sample indicates that said individual is not an individual who will not benefit from said treatment. In some embodiments, provided herein are methods of identifying an individual (e.g., a human) with colorectal cancer who would benefit from treatment comprising administration of an ATR inhibitor, the method comprising detecting in a sample from the individual Detect one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1 , PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30 , PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11 , NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DI DO1 , CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PA RP14 , AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2 , CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more drug resistance genes selected from the following group One or more drug resistance abnormalities (such as drug resistance mutations): RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK 2. EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, where drug sensitivity abnormalities (eg, drug sensitivity mutations ) and drug resistance abnormalities (such as drug resistance mutations) above a threshold level, the individual is identified as an individual who may benefit from treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，其中所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在表明投予DNA損傷劑(例如PARPi或ATRi)的治療是對所述個體合適的治療。在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1, 其中所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在表明包含投予DNA損傷劑(例如PARPi或ATRi)的治療作是對所述個體不合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1, 其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分確定了包含投予DNA損傷劑(例如PARPi或ATRi)作為合適的治療的個體的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2 , GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS , RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6 , RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2 , USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18 , RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB , ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2 , ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G 2C , CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1 , UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, wherein one or more of the samples are sensitive to the drug The presence of a sexual abnormality (eg, a drug sensitivity mutation) indicates that treatment with a DNA damaging agent (eg, PARPi or ATRi) is an appropriate treatment for the individual. In some embodiments, provided herein is a method of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more resistant One or more resistance abnormalities (eg, resistance mutations) in drug genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1 , LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN , PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1 , EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5 , BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG 1 , ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1 , PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C , CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, B RD4 , EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1 , PKMYT1, SIDT2, and GAB1, wherein the presence of one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample indicates that a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) is inappropriate for the individual Treatment. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2 , GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS , RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6 , RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2 , USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18 , RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB , ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2 , ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G 2C , CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1 , UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more selected from the following group One or more resistance abnormalities (eg, resistance mutations) in resistance genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, Plec, Crebbp, RELA, E2F3, ITIH6, BRPF3, Anapc7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, MYH9, FGF19, EIF4E2, EIF4E2, EIF4E2, EIF4E2, EIF4E2, EIF4E2 , TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SK P2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, wherein a composite score of drug susceptibility abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) above a threshold level determines the inclusion of DNA damaging agents (such as PARPi or ATRi) as an appropriate treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B, 其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分表明包含投予DNA損傷劑(例如PARPi或ATRi)的治療是對所述個體合適的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2 , GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS , RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6 , RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2 , USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18 , RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB , ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2 , ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G 2C , CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1 , UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more selected from the following group One or more resistance abnormalities (eg, resistance mutations) in resistance genes: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, in which drug sensitivity abnormalities above the threshold level (such as drug sensitivity mutation ) and a resistance abnormality (eg, a resistance mutation) indicates that a treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi) is an appropriate treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM, 其中所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在表明投予DNA損傷劑(例如PARPi或ATRi)的治療是對所述個體合適的治療。在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B, 其中所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在表明包含投予DNA損傷劑(例如PARPi或ATRi)的治療作是對所述個體不合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B, 其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分表明包含投予DNA損傷劑(例如PARPi或ATRi)的治療是對所述個體合適的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of selecting treatment for an individual (eg, a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drugs selected from the group consisting of One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in sensitivity genes: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, where one or more drug sensitivity is abnormal (eg, drug sensitivity mutation) in the sample The presence of indicates that administration of a DNA damaging agent such as PARPi or ATRi is an appropriate treatment for the individual. In some embodiments, provided herein is a method of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more resistant One or more resistance abnormalities (eg, resistance mutations) in drug genes: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL , PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein one or more drug resistance abnormalities (such as drug resistance mutations) ) indicates that a treatment comprising administration of a DNA damaging agent such as PARPi or ATRi is an inappropriate treatment for the individual. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM , KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and one or more drug resistance genes selected from the following group Abnormalities (eg resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, among them, drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) above the threshold level ) indicates that treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi) is an appropriate treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1, 其中所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在表明包含投予PARP抑制劑的治療是對所述個體的合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX, 其中所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在表明包含投予PARP抑制劑的治療是對所述個體的合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19, 其中所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在表明包含投予PARP抑制劑的治療是對所述個體不合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在表明包含投予PARP抑制劑的治療是對所述個體不合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19, 其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分表明包含投予PARP抑制劑的治療是對所述個體合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1, 其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分表明包含投予PARP抑制劑的治療是對所述個體合適的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2 , GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS , RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6 , RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2 , USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, wherein the samples The presence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in , indicates that a treatment comprising administration of a PARP inhibitor is an appropriate treatment for the individual. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL , EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1 , GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, wherein the presence of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in the sample indicates that treatment comprising administration of a PARP inhibitor is appropriate for the individual treat. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistance selected from the group consisting of One or more resistance abnormalities (eg, resistance mutations) in genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, where The presence of one or more resistance abnormalities (eg, resistance mutations) in the sample indicates that treatment comprising administration of a PARP inhibitor is an inappropriate treatment for the individual. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistance selected from the group consisting of One or more resistance abnormalities (eg, resistance mutations) in genes: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1 , HSP90B1 , CCNA1 , and RBL1 , wherein the presence of one or more resistance abnormalities (eg, resistance mutations) in the sample indicates that treatment comprising administration of a PARP inhibitor is an inappropriate treatment for the individual. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2 , GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS , RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6 , RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2 , USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and one or more One or more drug resistance abnormalities (such as drug resistance mutations) in a drug resistance gene selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, wherein a composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) above a threshold level indicates that treatment comprising administration of a PARP inhibitor is appropriate for the individual appropriate treatment. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL , EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1 , GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, where drug sensitivity abnormalities (such as drug sensitivity mutations) above threshold levels and A composite score of resistance abnormalities (eg, resistance mutations) indicates that treatment comprising administration of a PARP inhibitor is an appropriate treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B, 其中所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在表明包含投予ATR抑制劑的治療是對所述個體合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1, 其中所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在表明包含投予ATR抑制劑的治療是對所述個體不合適的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1, 其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分表明包含投予ATR抑制劑的治療是對所述個體合適的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A , EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB , PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1 , HSPG2, TRIB3, PPA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, Mapk14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, Anapc7, DIDO1, CDK2,, CDK2,, ACTB, GFRA1, TP53bp1, LRRIQ1, STAG1 , ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, T ENM4 , PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM , PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, wherein the presence of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in the sample indicates that administration of ATR Treatment with inhibitors is an appropriate treatment for the individual. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistance selected from the group consisting of One or more resistance abnormalities (eg, resistance mutations) in genes: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DO CK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, wherein one or more of the samples are resistant to The presence of a drug abnormality (eg, a drug resistance mutation) indicates that a treatment comprising administration of an ATR inhibitor is an inappropriate treatment for the individual. In some embodiments, provided herein are methods of selecting treatment for an individual (e.g., a human) with colorectal cancer, the method comprising detecting in a sample from the individual one or more drug-sensitive agents selected from the group consisting of: Drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more sex genes: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A , EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB , PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1 , HSPG2, TRIB3, PPA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, Mapk14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, Anapc7, DIDO1, CDK2,, CDK2,, ACTB, GFRA1, TP53bp1, LRRIQ1, STAG1 , ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, T ENM4 , PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM , PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group ): RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as resistance Drug mutation) indicates that treatment comprising administration of an ATR inhibitor is an appropriate treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B;和(b)生成報告，其中所述報告包含至少部分基於所述樣本中存在的一種或多種藥物敏感性異常(例如藥物敏感性突變)而為所述個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇包括包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1；和(b)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在為個體確定的一種或多種治療選擇，其中一種或多種治療選擇不包括包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B; (b)在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1；和(c)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇包括包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，所述方法進一步包含獲得個體樣本中的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a plurality of drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6 KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB 2. CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B; and (b) generating a report, wherein the report includes one or more treatment options determined for the individual based at least in part on the presence of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in the sample, wherein the One or more treatment options include treatments comprising administration of a DNA damaging agent such as PARPi or ATRi. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (e.g., a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more One or more resistance abnormalities (eg, resistance mutations) in resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC , RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF , WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1 , CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A , FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9 , CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1 D. , TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1 , CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB , NLRC5 , RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2 , Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1; and (b) generating a report, wherein the report comprises determining for an individual based at least in part on the presence of one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample One or more treatment options, wherein the one or more treatment options do not include treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, provided herein are methods of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the methods comprising: (a) detecting one or more treatment options in a sample from the individual One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a drug sensitivity gene selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4 , CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4 , NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1 , FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1 , ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300 , KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1 , RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5 , BMP8B , MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR 1 , FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP , PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B; (b ) detecting in a sample from said individual one or more drug resistance abnormalities (eg, drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP 2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B , EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1; and (c) generating a report, wherein the report comprises at least in part based on one or One or more treatment options determined for the individual based on the presence of multiple drug sensitivity abnormalities (eg, drug sensitivity mutations) and one or more drug resistance abnormalities (eg, drug resistance mutations), wherein the one or more treatment options include comprising Treatment with a DNA damaging agent such as PARPi or ATRi is administered. In some embodiments, the method further comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B; (b)在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B；和(c)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇包括包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，所述方法還包含獲得個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a plurality of drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6 KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB 2. CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, ( b) detecting in a sample from said individual one or more drug resistance abnormalities (eg drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2 , SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2 , PARP1 , and EIF4B; and (c) generating a report, wherein the report includes one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) and one or more drug resistance abnormalities (e.g., drug resistance mutations) based at least in part on the sample. mutation), wherein the one or more treatment options include treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the method further comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM;和(b)生成報告，其中所述報告包含至少部分基於所述樣本中存在的一種或多種藥物敏感性異常(例如藥物敏感性突變)而為所述個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇包括包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B；和(b)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在為個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇不包括包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM; (b)在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B；和(c)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇包括包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，所述方法進一步包含獲得個體樣本中的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a plurality of drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM; and (b) generating a report, wherein the report comprising one or more treatment options determined for the individual based at least in part on the presence of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in the sample, wherein the one or more treatment options comprise administering DNA Treatment of damaging agents such as PARPi or ATRi. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (e.g., a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more One or more resistance abnormalities (eg, resistance mutations) in resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC , GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B; and (b) generate a report wherein the The report comprises one or more treatment options determined for the individual based at least in part on the presence of one or more drug resistance abnormalities (e.g., drug resistance mutations) in said sample, wherein said one or more treatment options do not include administration of a DNA damaging agent ( For example the treatment of PARPi or ATRi). In some embodiments, provided herein are methods of determining one or more treatment options for an individual (e.g., a human) with colorectal cancer, the methods comprising: (a) detecting one or more treatment options in a sample from the individual One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B , DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM; (b) detection of Detect one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, and (c) generate a report, wherein the report comprises the determination for the individual based at least in part on the presence of one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) and one or more drug resistance abnormalities (e.g. drug resistance mutations) in the sample One or more treatment options, wherein the one or more treatment options comprise treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the method further comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1;和(b)生成報告，其中所述報告包含至少部分基於所述樣本中存在的一種或多種藥物敏感性異常(例如藥物敏感性突變)而為所述個體確定的一種或多種治療選擇，其中一種或多種治療選擇包括包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX;和(b)生成報告，其中所述報告包含至少部分基於所述樣本中存在的一種或多種藥物敏感性異常(例如藥物敏感性突變)而為所述個體確定的一種或多種治療選擇，其中一種或多種治療選擇包括包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19；和(b)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中一種或多種治療選擇不包括包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1；和(b)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中一種或多種治療選擇不包括包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1; (b)在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19；和(c)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和一種或多種耐藥異常(例如耐藥突變)的存在為個體確定的一種或多種治療選擇，其中一種或多種治療選擇包括包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX; (b)在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1; 以及(c)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇包括包含投予PARP抑制劑的治療。在一些實施方案中，所述方法進一步包含獲得個體樣本中的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a plurality of drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1; and (b) generating a report, wherein the report comprises one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) identified for the individual based at least in part on the presence of one or more drug sensitivity abnormalities in the sample Treatment options, wherein one or more treatment options include treatment comprising administering a PARP inhibitor. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the methods comprising: (a) detecting one or more treatment options in a sample from the individual One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a drug sensitivity gene selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1 , WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7 , TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX; and (b) generating a report, wherein the report includes one or more drug sensitivity abnormalities based at least in part on the presence of the sample (e.g. drug susceptibility mutation), wherein one or more treatment options comprises a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (e.g., a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more One or more resistance abnormalities (eg, resistance mutations) in resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC , RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF , WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1 , CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A , FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1 , SIDT2, and FGF19; and (b) generating a report, wherein the report includes one or more treatments determined for the individual based at least in part on the presence of one or more drug resistance abnormalities (eg, drug resistance mutations) in the sample Selection, wherein one or more treatment options do not include treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (e.g., a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more One or more drug resistance abnormalities (such as drug resistance mutations) in drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5 , IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3 , E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1; and (b) generating a report, wherein the report includes an identification based at least in part on the presence of one or more resistance abnormalities (e.g., resistance mutations) in the sample. One or more treatment options identified for the individual, wherein one or more treatment options do not include treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the methods comprising: (a) detecting one or more treatment options in a sample from the individual One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a drug sensitivity gene selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4 , CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4 , NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1 , FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1 、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1 , and STAP1; (b) detecting one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19; and (c) generating a report, wherein the report includes a drug based at least in part on one or more drugs in the sample The presence of a susceptibility abnormality (e.g., a drug sensitivity mutation) and one or more drug resistance abnormalities (e.g., a drug resistance mutation) is one or more treatment options identified for the individual, wherein the one or more treatment options include treatment comprising administration of a PARP inhibitor . In some embodiments, provided herein are methods of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the methods comprising: (a) detecting one or more treatment options in a sample from the individual One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a drug sensitivity gene selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1 , WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7 , TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX; (b) detecting one or more of one or more drug resistance genes selected from the following group in a sample from said individual Drug resistance abnormalities (such as drug resistance mutations): PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1; and (c) generating a report, wherein the report comprises a report based at least in part on one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) and one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample There is one or more treatment options determined for the individual, wherein the one or more treatment options include treatment comprising administering a PARP inhibitor. In some embodiments, the method further comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B;和(b)生成報告，其中所述報告包含至少部分基於所述樣本中存在的一種或多種藥物敏感性異常(例如藥物敏感性突變)而為所述個體確定的一種或多種治療選擇，其中一種或多種治療選擇包括包含投予ATR抑制劑的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1；和(b)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中一種或多種治療選擇不包括包含投予ATR抑制劑的治療。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B; (b)在來自所述個體的樣本中偵測一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1；和(c)生成報告，其中所述報告包含至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和一種或多種耐藥異常(例如耐藥突變)的存在而為所述個體確定的一種或多種治療選擇，其中所述一種或多種治療選擇包括包含投予ATR抑制劑的治療。在一些實施方案中，所述方法進一步包含獲得個體樣本中的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a plurality of drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, A XL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B; and (b) generating a report, wherein said report comprises One or more treatment options determined for the individual based on the presence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in the sample, wherein the one or more treatment options include treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (e.g., a human) with colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more One or more drug resistance abnormalities (such as drug resistance mutations) in drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168 , MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2 , CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1 , IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2 , PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1 ( b) generating a report, wherein the report comprises one or more treatment options determined for the individual based at least in part on the presence of one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample, wherein one or more treatment options Treatments involving administration of ATR inhibitors were excluded. In some embodiments, provided herein are methods of determining one or more treatment options for an individual (eg, a human) with colorectal cancer, the methods comprising: (a) detecting one or more treatment options in a sample from the individual One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1 , SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2 , NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1 , HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB , GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL , GRB2 , CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5 , TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B; (b) detecting one or more selected One or more drug resistance abnormalities (such as drug resistance mutations) in drug resistance genes from the following group: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CT NNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1; and (c ) generating a report, wherein the report comprises a report for the individual based at least in part on the presence of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) and one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample One or more treatment options are identified, wherein the one or more treatment options include treatment comprising administration of an ATR inhibitor. In some embodiments, the method further comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，其中回應所述獲知：(i)所述個體被列為接受包含投予DNA損傷劑(例如PARPi或ATRi)的治療的候選者；和/或(ii)將所述個體鑒定為可對包含投予DNA損傷劑(例如PARPi或ATRi)的治療應答。在一些實施方案中，本文提供的是為患有結直腸癌的個體(例如人)排除某種治療的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中回應所述獲知：(i)所述個體被列為不接受包含投予DNA損傷劑(例如PARPi或ATRi)的治療的候選者；和/或(ii)所述個體被確定為不可對包含投予DNA損傷劑(例如PARPi或ATRi)的治療應答。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中回應所述獲知：(i)所述個體被列為接受包含投予DNA損傷劑(例如PARPi或ATRi)的治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予DNA損傷劑(例如PARPi或ATRi)的治療應答。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., a human) suffering from colorectal cancer, comprising knowing one or more of a drug sensitivity gene selected from a sample of the individual or multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, Z NF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, wherein in response to the learning: (i) the individual is listed as a candidate for treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi); and/or (ii) identifying the individual as responsive to treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., a human) suffering from colorectal cancer, comprising knowing one or more drug resistance genes selected from the group consisting of one or more drug resistance genes in a sample of the individual or multiple resistance abnormalities (such as resistance mutations): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, Plec, Crebbp, RELA, E2F3, ITIH6, BRPF3, Anapc7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MyH14, RASL10B, MyH9, FGF19, TNFRSF17, CUL9, CD C25A, KMT2D, Foxg1, Arid1a, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DB F4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, wherein in response to the learning: (i) the individual is listed as a candidate not to receive treatment comprising administration of a DNA damaging agent (such as PARPi or ATRi); and/or (ii) the individual is determined to be Unable to respond to treatment comprising administration of a DNA damaging agent such as PARPi or ATRi. In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of a drug sensitivity gene selected from the group consisting of one or more of the drug sensitivity genes in a sample of the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance genes selected from the group below or multiple resistance abnormalities (such as resistance mutations): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, Plec, Crebbp, RELA, E2F3, ITIH6, BRPF3, Anapc7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MyH14, RASL10B, MyH9, FGF19, TNFRSF17, CUL9, CD C25A, KMT2D, Foxg1, Arid1a, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DB F4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, wherein in response to the learning: (i) the individual is listed as a candidate for treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi); and/or (ii) the individual is identified as having Response to treatment comprising administration of a DNA damaging agent such as PARPi or ATRi. In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知：(i)所述個體被列為接受包含投予DNA損傷劑(例如PARPi或ATRi)治療的候選者；和/或(ii)將所述個體鑒定為可對包含投予DNA損傷劑(例如PARPi或ATRi)的治療應答。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of a drug sensitivity gene selected from the group consisting of one or more of the drug sensitivity genes in a sample of the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance genes selected from the group below or multiple resistance abnormalities (such as resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein in response to the learning: (i) the individual is listed as receiving DNA-damaging and/or (ii) identifying the individual as responding to a treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，其中回應所述獲知：(i)所述個體被列為接受包含投予DNA損傷劑(例如PARPi或ATRi)治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予DNA損傷劑(例如PARPi或ATRi)的治療應答。在一些實施方案中，本文提供了一種為患有結直腸癌的個體(例如人)排除某種治療的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知：(i)所述個體被列為不接受包含投予DNA損傷劑(例如PARPi或ATRi)治療的候選者；和/或(ii)所述個體被鑒定為不可對包含投予DNA損傷劑(例如PARPi或ATRi)的治療應答。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM,和一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知：(i)所述個體被列為接受包含投予DNA損傷劑(例如PARPi或ATRi)治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予DNA損傷劑(例如PARPi或ATRi)的治療應答。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of said individual Abnormal drug sensitivity (e.g., drug-sensitive mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, wherein in response to the learning: (i) the individual is listed as receiving a DNA damaging agent (such as PARPi or ATRi ) a candidate for treatment; and/or (ii) the individual is identified as responsive to a treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., a human) with colorectal cancer, comprising knowing one or more drug resistance genes selected from the group consisting of one or more drug resistance genes in a sample of said individual or multiple resistance abnormalities (such as resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein in response to the learning: (i) the individual is listed as not receiving DNA comprising a candidate for treatment with a damaging agent (eg, PARPi or ATRi); and/or (ii) the individual is identified as non-responsive to a treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of a drug sensitivity gene selected from the group consisting of one or more of the drug sensitivity genes in a sample of the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1 , GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group ): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein in response to said learning: (i) the individual is listed as a candidate for treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) and/or (ii) the individual is identified as responding to a treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，其中回應所述獲知：(i)所述個體被列為接受包含投予PARP抑制劑治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予PARP抑制劑的治療應答。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，其中回應所述獲知：(i)所述個體被列為接受包含投予PARP抑制劑治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予PARP抑制劑的治療應答。在一些實施方案中，本文提供的是為患有結直腸癌的個體(例如人)排除某種治療的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，其中回應所述獲知：(i)所述個體被列為不接受包含投予PARP抑制劑的治療的候選者；和/或(ii)所述個體被鑒定為不可對包含投予PARP抑制劑的治療應答。在一些實施方案中，本文提供的是為患有結直腸癌的個體(例如人)排除某種治療的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中回應所述獲知：(i)所述個體被列為不接受包含投予PARP抑制劑的治療的候選者；和/或(ii)所述個體被鑒定為不可對包含投予PARP抑制劑的治療應答。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中的一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，其中回應所述獲知：(i)所述個體被列為接受包含投予PARP抑制劑治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予PARP抑制劑的治療應答。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中回應所述獲知：(i)所述個體被列為接受包含投予PARP抑制劑治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予PARP抑制劑的治療應答。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of said individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, which responded to the knowledge that: (i) The individual is listed as a candidate for treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as responding to treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of said individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, wherein in response to the learning: (i) the individual is listed as a candidate for treatment comprising administering a PARP inhibitor; and/or (ii) the individual is identified as a candidate for treatment comprising administering a PARP Treatment response to inhibitors. In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., a human) suffering from colorectal cancer, comprising knowing one or more drug resistance genes selected from the group consisting of one or more drug resistance genes in a sample of the individual or multiple resistance abnormalities (eg, resistance mutations) PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2 , PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1 , BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1 , CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1 , PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, which responded to the knowledge that: (i) the individual is listed as a candidate not to receive a treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as non-responsive to a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., a human) suffering from colorectal cancer, comprising knowing one or more drug resistance genes selected from the group consisting of one or more drug resistance genes in a sample of the individual or multiple resistance abnormalities (such as drug resistance mutations) PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2 , KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1 , and RBL1, wherein in response to the learning: (i) the individual is listed as a candidate not to receive treatment comprising administering a PARP inhibitor; and/or (ii) the individual is identified as ineligible for treatment comprising administering a PARP inhibitor; Therapeutic response to PARP inhibitors. In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of a drug sensitivity gene selected from the group consisting of one or more of the drug sensitivity genes in a sample of the individual or Multiple drug sensitivity abnormalities (eg, drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and one or more selected from the following group One or more resistance abnormalities (eg, resistance mutations) in resistance genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19 , wherein in response to the learning: (i) the individual is listed as a candidate for treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as a candidate for treatment comprising administration of a PARP inhibitor answer. In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of said individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2 , GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1 , CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, wherein in response to the learning: (i) the individual is listed as receiving treatment comprising administration of a PARP inhibitor candidate; and/or (ii) the individual is identified as responsive to a treatment comprising administration of a PARP inhibitor. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，其中回應所述獲知：(i)所述個體被列為接受包含投予ATR抑制劑治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予ATR抑制劑的治療應答。在一些實施方案中，本文提供的是為患有結直腸癌的個體(例如人)排除某種治療的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中回應所述獲知：(i)所述個體被列為不接受包含投予ATR抑制劑的治療的候選者；和/或(ii)所述個體被鑒定為不可對包含投予ATR抑制劑的治療應答。在一些實施方案中，本文提供了為患有結直腸癌的個體(例如人)選擇治療的方法，包含獲知個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中回應所述獲知：(i)所述個體被列為接受包含投予ATR抑制劑治療的候選者；和/或(ii)所述個體被鑒定為可對包含投予ATR抑制劑的治療應答。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of selecting a treatment for an individual (eg, a human) suffering from colorectal cancer, comprising knowing one or more of one or more drug sensitivity genes selected from the group consisting of in a sample of said individual Drug sensitivity abnormalities (eg, drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A , SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, wherein in response to the learning: (i) the individual is listed as a candidate for treatment comprising administering an ATR inhibitor; and/or (ii) The individual is identified as responsive to treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., a human) suffering from colorectal cancer, comprising knowing one or more drug resistance genes selected from the group consisting of one or more drug resistance genes in a sample of the individual or multiple resistance abnormalities (such as resistance mutations): RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, Dock1, Znf469, PLA2G12B, EGFR, WDFY4, USP9X, Gal3st4, Kiaa1217, MAPK3, CBFB, NLRC5, SKP2, BRD4, MYH9, DBF4, CTNNBIP, CTNNBIP, CTNNBIP, CTNNBIP 1. GNA11, SCN3A, Dock6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, wherein in response to said learning: (i) said individual was is listed as a candidate not to receive a treatment comprising the administration of an ATR inhibitor; and/or (ii) the individual is identified as non-responsive to a treatment comprising the administration of an ATR inhibitor. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., a human) suffering from colorectal cancer, comprising knowing in a sample from the individual one or more drug sensitivity genes selected from the group consisting of one or more drug sensitivity genes Sexual abnormalities (eg, drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, Z NF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, One or more drug resistance abnormalities (such as drug resistance mutations) in UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2 , TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3 , PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R , MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1 . 17 , MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B , FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, wherein in response to the learning: (i) the individual is listed as a candidate for treatment comprising administration of an ATR inhibitor; and/or (ii ) said individual identified as responsive to a treatment comprising administration of an ATR inhibitor. In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予DNA損傷劑(例如PARPi或ATRi)治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)： PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用DNA損傷劑(例如PARPi或ATRi)治療後具有更長的生存期。在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予DNA損傷劑(例如PARPi或ATRi)治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用DNA損傷劑(例如PARPi或ATRi)治療後具有更長的生存期。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a DNA damaging agent (e.g., PARPi or ATRi), the method comprising knowing the One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T in a sample from an individual , FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B , CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1 , CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ , BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1 , DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3 , NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK 1G1 , DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14 , AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5 , TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, wherein responsive to said learning, said individual is predicted to be on DNA damaging agents (e.g., e.g. PARPi or ATRi) had a longer survival period after treatment. In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a DNA damaging agent (e.g., PARPi or ATRi), the method comprising knowing the One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T in a sample from an individual , FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B , CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1 , CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ , BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1 , DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3 , NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK 1G1 , DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14 , AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5 , TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGR B2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, which respond to said learning, are not associated with said one or more drug sensitivity abnormalities (e.g., drug sensitive Such individuals are predicted to have a longer survival after treatment with a DNA damaging agent (eg, PARPi or ATRi) than individuals with DNA-damaging mutations). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予DNA損傷劑(例如PARPi或ATRi)治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用DNA損傷劑(例如PARPi或ATRi)治療後具有更長的生存期。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a DNA damaging agent (e.g., PARPi or ATRi), the method comprising knowing the One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T in a sample from an individual , FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B , CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1 , CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ , BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1 , DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3 , NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK 1G1 , DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14 , AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5 , TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, where In response to said learning, predicting that said individual is being treated with a DNA damaging agent (e.g., PARPi or ATRi) compared to an individual who does not have said one or more drug sensitivity abnormalities (e.g., a drug sensitivity mutation) in an equivalent sample have a longer lifespan. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予DNA損傷劑(例如PARPi或ATRi)治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)： GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用DNA損傷劑(例如PARPi或ATRi)治療後具有更長的生存期。在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予DNA損傷劑(例如PARPi或ATRi)治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用DNA損傷劑(例如PARPi或ATRi)治療後具有更長的存活率。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a DNA damaging agent (e.g., PARPi or ATRi), the method comprising knowing the One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2 in a sample from an individual , NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, which responded to said notification, The individual is predicted to have a longer DNA-damaging agent (e.g., PARPi or ATRi) after treatment with a DNA-damaging agent (e.g., PARPi or ATRi) than an individual without the one or more drug sensitivity abnormalities (e.g., a drug sensitivity mutation) in an equivalent sample lifetime. In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a DNA damaging agent (e.g., PARPi or ATRi), the method comprising knowing the One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2 in a sample from an individual , NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and one or more selected One or more drug resistance abnormalities (such as drug resistance mutations) in drug resistance genes from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, which responded to the knowledge, were compared in equivalent samples Said individual is predicted to have a longer survival rate after treatment with a DNA damaging agent (eg, PARPi or ATRi) compared to an individual in the group who does not have said one or more drug sensitivity abnormalities (eg, a drug sensitivity mutation). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予PARP抑制劑治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)： PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用PARP抑制劑治療後具有更長的生存期。在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予PARP抑制劑治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用PARP抑制劑治療後具有更長的生存期。在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予PARP抑制劑治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用PARP抑制劑治療後具有更長的生存期。在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予PARP抑制劑治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用PARP抑制劑治療後具有更長的生存期。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a PARP inhibitor, the method comprising knowing one or more One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4 , CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4 , NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1 , FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1 、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1 , and STAP1 , wherein responsive to said learning, said individual is predicted to respond to treatment with a PARP inhibitor compared to an individual who does not have said one or more drug sensitivity abnormalities (e.g., a drug sensitivity mutation) in an equivalent sample have a longer lifespan. In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a PARP inhibitor, the method comprising knowing one or more One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a drug sensitivity gene selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1 , WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7 , TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, wherein responding to said learning, and not having said one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in equivalent samples The individual is predicted to have a longer survival period after treatment with a PARP inhibitor compared to an individual of . In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a PARP inhibitor, the method comprising knowing one or more One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a drug sensitivity gene selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4 , CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4 , NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1 , FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1 、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1 , and STAP1, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, wherein in response to said learning, compared to individuals who do not have said one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in an equivalent sample, The individual is predicted to have a longer survival after treatment with a PARP inhibitor. In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering a PARP inhibitor, the method comprising knowing one or more One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a drug sensitivity gene selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1 , WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7 , TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, which responded to the knowledge that, with the Said individual is predicted to have a longer survival period following treatment with a PARP inhibitor compared to an individual in a valid sample who does not have said one or more drug sensitivity abnormalities (eg, a drug sensitivity mutation). In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予ATR抑制劑治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用ATR抑制劑治療後具有更長的生存期。在一些實施方案中，本文提供了一種預測患有結直腸癌並經包含投予ATR抑制劑治療的個體(例如人)的生存期的方法，所述方法包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用ATR抑制劑治療後具有更長的生存期。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering an ATR inhibitor, the method comprising knowing one or more One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1 , SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2 , NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1 , HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB , GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL , GRB2 , CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5 , TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, wherein responding to said learning, and not having said one or Individuals with multiple drug sensitivity abnormalities (eg, drug sensitivity mutations) are predicted to have longer survival after treatment with an ATR inhibitor. In some embodiments, provided herein is a method of predicting survival in an individual (e.g., a human) having colorectal cancer treated comprising administering an ATR inhibitor, the method comprising knowing one or more One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1 , SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2 , NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1 , HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB , GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL , GRB2 , CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5 , TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more drug resistance genes selected from the group below Drug resistance abnormalities (eg resistance mutations): RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP , ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, which responded to the knowledge, did not have all The individual is predicted to have a longer survival period after treatment with an ATR inhibitor compared to an individual with one or more drug sensitivity abnormalities (eg, a drug sensitivity mutation). In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性測試的個體(例如人)的方法，包含：獲取識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊：個體中的PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，其中所述資訊將所述個體鑒定為適合於包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊： PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中所述資訊將所述個體鑒定為不適合包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取識別所述個體中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及所述個體中一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中所述資訊(例如，超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分)將所述個體鑒定為適合包含投予DNA損傷劑(例如PARPi或ATRi)治療的個體。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is an assessment of an individual having colorectal cancer, suspected of having colorectal cancer, being detected for colorectal cancer, being treated for colorectal cancer, or being tested for colorectal cancer susceptibility (e.g. A method for humans), comprising: obtaining information identifying one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, HPRT1, DNAH11, DPM2, DPM2, DPM2 , PTPN11, Wnt7b, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, wherein the information identifies the individual as suitable for treatment comprising administration of a DNA damaging agent such as PARPi or ATRi. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug resistance abnormalities (e.g. drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13 C. PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, Dock1, Znf469, PLA2G12B, EGFR, WDFY4, USP9X, Gal3st4, Kiaa1217, Mapk3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, R OCK2, COMP, Arid2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, wherein the information identifies the individual as unsuitable for comprising administering DNA Treatment of damaging agents such as PARPi or ATRi. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in said individual in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39 , RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2 , DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B , TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2 , WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1 , CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30 , ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2 , DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42 , DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTO A , DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B , RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP 5. NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2 , RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, wherein the information (e.g., exceeding a threshold A combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) at the level identifies the individual as an individual suitable for treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及所述個體中一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中所述資訊(例如，超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分)將所述個體鑒定為適合包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39 , RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2 , DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B , TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2 , WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1 , CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30 , ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2 , DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42 , DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTO A , DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B , RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein the information (e.g., drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) above a threshold level Composite score) identifies the individual as suitable for treatment comprising administration of a DNA damaging agent such as PARPi or ATRi. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，其中所述資訊將所述個體鑒定為適合包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取識別所述個體中一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊： RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中所述資訊將所述個體鑒定為不適合包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，本文提供的是評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，以及所述個體中一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中所述資訊(例如，超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分)將所述個體鑒定為適合包含投予DNA損傷劑(例如PARPi或ATRi)的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1 , YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A , ATM, YWHAE, and FANCM, wherein the information identifies the individual as suitable for treatment comprising administration of a DNA damaging agent (eg, PARPi or ATRi). In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information identifying one or more drug resistance abnormalities (e.g. drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein the information identifies the individual as unsuitable for treatment comprising administration of a DNA damaging agent such as PARPi or ATRi. In some embodiments, provided herein is the assessment of an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to, colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1 , YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A , ATM, YWHAE, and FANCM, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein the information (e.g., a composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) above a threshold level) identifies the individual as eligible Treatment comprising administration of a DNA damaging agent such as PARPi or ATRi. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，其中所述資訊將所述個體鑒定為適合包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，其中所述資訊將所述個體鑒定為適合包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊： PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，其中所述資訊將所述個體鑒定為不適合包含投予PARP抑制劑的治療。在一些實施方案中，本文提供的是評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊： PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中所述資訊將所述個體鑒定為不適合包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，以及所述個體中一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，其中所述資訊(例如，高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分)將所述個體鑒定為適合包含投予PARP抑制劑的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，以及所述個體中一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中所述資訊(例如，高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分)將所述個體鑒定為適合包含投予PARP抑制劑的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39 , RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2 , DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B , TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2 , WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A , RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, wherein the information identifies the individual as suitable for treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR , BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2 , HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, wherein the information identifies the individual as Treatment comprising administration of a PARP inhibitor is suitable. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug resistance abnormalities (e.g. drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, wherein the information identifies the individual as unsuitable for treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is the assessment of an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to, colorectal cancer (e.g. human) method comprising: obtaining information identifying one or more drug resistance abnormalities (e.g. drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, wherein the information identifies the individual as unsuitable for inclusion in the Treatment with PARP inhibitors. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39 , RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2 , DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B , TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2 , WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A , RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and one or more drug resistance abnormalities in one or more drug resistance genes selected from the following group in the individual ( For example drug resistance mutations): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, where the information (e.g., above a threshold level A composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) of ) identifies the individual as suitable for treatment comprising administering a PARP inhibitor. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR , BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2 , HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more of said individuals One or more drug resistance abnormalities (such as drug resistance mutations) in drug resistance genes from the following group: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, wherein the information (e.g., a combination of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) above a threshold level) score) identifies the individual as suitable for treatment comprising administration of a PARP inhibitor. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：所述個體中獲取識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，其中所述資訊將所述個體鑒定為適合包含投予ATR抑制劑的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊： RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中所述資訊將所述個體鑒定為不適合包含投予ATR抑制劑的治療。在一些實施方案中，本文提供了一種評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含：獲取所述個體中識別一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊： ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，以及所述個體中一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中所述資訊(例如，超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分)將所述個體鑒定為適合包含投予ATR抑制劑的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining in said individual information identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE , NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5 , DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP 2 , PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1 , AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN1 1 , WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA- B, wherein the information identifies the individual as suitable for treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information identifying one or more drug resistance abnormalities (e.g. drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, wherein the information identifies the individual as unsuitable for a treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method for assessing an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to colorectal cancer (e.g. human) method comprising: obtaining information in said individual identifying one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE , NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5 , DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP 2 , PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1 , AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN1 1 , WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA- B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET , SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, wherein the information (e.g., a composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) above a threshold level) identifies the individual A treatment comprising administering an ATR inhibitor is suitable. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體具有降低的結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或不良預後的風險。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中回應所述獲知，與不具有一種或多種耐藥異常(例如耐藥突變)的個體相比，預測所述個體具有的直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良風險增加。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B,以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1 in a sample of said individual , ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1 , NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1 , ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4 , RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B , PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4 , NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2 , TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP 12. LARP4B , KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK , TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D , PMS2, MSH6, MSH2, MLH1, and HLA-B, wherein, in response to the learning, the individual is predicted to have a reduced outcome compared to an individual without one or more drug sensitivity abnormalities (e.g., a drug sensitivity mutation) Risk of rectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, the method of people), comprising knowing one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual sample: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TEN M3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, which respond to the learning, are associated with not having one or more drug resistance abnormalities (e.g., drug resistance mutation) are predicted to have an increased risk of rectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1 in a sample of said individual , ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1 , NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1 , ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4 , RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B , PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4 , NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2 , TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP 12. LARP4B , KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK , TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D , PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2 G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, which respond to the learning, are associated with the absence of one or more drug sensitivity abnormalities ( For example, a drug sensitivity mutation) is predicted to have a reduced risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis in said individual. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1 in a sample of said individual , ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1 , NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1 , ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4 , RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B , PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4 , NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2 , TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP 12. LARP4B , KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK , TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D , PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, wherein responsive to said learning, predict colorectal cancer recurrence, invasive colorectal cancer in said individual compared to individuals without one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) reduced risk of cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知，與不具有一種或多種耐藥異常(例如耐藥突變)的個體相比，預測個體具有增加的結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或不良預後的風險。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN in a sample of said individual , PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE , and FANCM, wherein responsive to said learning, predicting colorectal cancer recurrence, invasive colorectal cancer, anticancer treatment in said individual compared to individuals without one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) Reduced risk of resistance or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for humans), comprising knowing one or more drug resistance abnormalities (for example, drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2 in said individual sample , SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2 , PARP1, and EIF4B, wherein in response to the knowledge, the individual is predicted to have increased colorectal cancer recurrence, invasive colorectal cancer, anticancer Risk of treatment resistance or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN in a sample of said individual , PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE , and FANCM, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, where Responsive to said learning, predicting colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis in said individual compared to individuals without one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) risk reduction. In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體具有降低的結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或不良預後的風險。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，其中回應所述獲知，與不具有一種或多種耐藥異常(例如耐藥突變)的個體相比，預測所述個體患結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險增加。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中回應所述獲知，與不具有一種或多種耐藥異常(例如耐藥突變)的個體相比，預測所述個體患結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險增加。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)： PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1 in a sample of said individual , ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1 , NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1 , ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4 , RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL , EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, wherein in response to the learning, compared to individuals without one or more drug sensitivity abnormalities (eg, drug sensitivity mutations), the predicted The individual has a reduced risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1 in a sample of said individual , FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2 , CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, which respond to the learning, are associated with not having one or more drug-sensitive The individual is predicted to have a reduced risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis compared to individuals with a sex abnormality such as a drug sensitivity mutation. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, the method of people), comprising knowing one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual sample: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, wherein in response to the learning, predicted The individual is at increased risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, the method of people), comprising knowing one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual sample: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, which respond to the learning, are associated with not having one or more resistance abnormalities (e.g. resistance mutations) are predicted to be at increased risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1 in a sample of said individual , ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1 , NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1 , ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4 , RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL , EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, which respond to the learning, are associated with the absence of one or more drug sensitivity abnormalities (e.g., drug Sensitivity mutations) are predicted to have a reduced risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1 in a sample of said individual , FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2 , CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance genes selected from the group below One or more drug resistance abnormalities (such as drug resistance mutations): PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, wherein responsive to said learning, predict colorectal cancer recurrence, invasive colorectal cancer, anticancer Reduced risk of treatment resistance or poor prognosis. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中的一種或多種選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中回應所述獲知，與不具有一種或多種耐藥異常(例如耐藥突變)的個體相比，預測所述個體患結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險增加。在一些實施方案中，本文提供了篩選患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體(例如人)的方法，包含獲知所述個體樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B, 以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1 in a sample of said individual , POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2 , DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4 , ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3 A , POLQ, HSP90AB1, CHD7, CKS2, AnAPC7, DIDO1, CDK2, Actb, GFRA1, TP53bp1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO90AA1, PAK1, YLPM1, CD C42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B , Kat2a, BCL2L1, KDM5C, Magi2, PTP4A3, Parp14, AXL, GRB2, CR1, Foxo1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, PEG3, INS, HPRT1, DNA, DNA, DNA H11, DPM2, PTPN11, Wnt7b, OTOA , DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, which responded The knowledge, compared to individuals without one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations), predicts that the individual has a reduced risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis . In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, the method of people), comprising knowing one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group in the individual sample: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK 3. CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, wherein responsive to said learning, said individual is predicted to suffer from colorectal cancer recurrence compared to an individual without one or more drug resistance abnormalities (e.g., drug resistance mutations) , invasive colorectal cancer, resistance to anticancer therapy, or increased risk of poor prognosis. In some embodiments, provided herein is the screening of individuals who have, are suspected of having, are being detected for, are being treated for, or are being detected for colorectal cancer susceptibility to, colorectal cancer ( For example, a method for a human) comprising knowing one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1 in a sample of said individual , POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2 , DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4 , ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3 A , POLQ, HSP90AB1, CHD7, CKS2, AnAPC7, DIDO1, CDK2, Actb, GFRA1, TP53bp1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO90AA1, PAK1, YLPM1, CD C42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B , Kat2a, BCL2L1, KDM5C, Magi2, PTP4A3, Parp14, AXL, GRB2, CR1, Foxo1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, PEG3, INS, HPRT1, DNA, DNA, DNA H11, DPM2, PTPN11, Wnt7b, OTOA A One or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G 2. DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1 , wherein responsive to said learning, the individual is predicted to have colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or The risk of poor prognosis is reduced. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，所述結直腸癌是：晚期結腸癌，惡性結腸癌，轉移性結腸癌，I、II、III或IV期結腸癌，以基因組不穩定性為特徵的結腸癌，以通路改變為特徵的結腸癌，根據結腸癌亞型(CCS)系統分類為CCS1、CCS2或CCS3的結腸癌，根據結直腸癌分配器(Colorectal Cancer Assigner，CRCA系統)分類為幹細胞樣、杯狀、炎性、過渡放大或腸上皮細胞亞型的結腸癌，根據結腸癌分子亞型(CCMS)系統分類為C1、C2、C3、C4、C5或C6亞型的結腸癌，根據CRC固有亞型(CRCIS)系統分類為A型、B型、或C型亞型的結腸癌，或根據結直腸癌亞型聯盟(CRCSC)分類系統分類為CMS1、CMS2、CMS3或CMS4的結腸癌中的任一種。在一些實施方案中，所述結腸癌具有MSI-高或MSI-低的微衛星不穩定性(MSI)狀態。在一些實施方案中，所述個體先前已接受治療(例如，化學療法、放射療法、手術或免疫調節療法)。在一些實施方案中，所述個體對先前的療法(例如，化學療法、放射療法、手術或免疫調節療法)沒有應答。In some embodiments, the colorectal cancer is: advanced colon cancer, malignant colon cancer, metastatic colon cancer, stage I, II, III or IV colon cancer, colon cancer characterized by genomic instability, pathway Changes to characteristic colon cancer, classified according to the Colon Cancer Subtype (CCS) system as CCS1, CCS2, or CCS3 Colon cancer, classified according to the Colorectal Cancer Assigner (CRCA system) as stem cell-like, goblet, inflammatory Colon cancer of the aggressive, transitional enlargement, or enterocyte subtype, classified according to the Colon Cancer Molecular Subtype (CCMS) system as C1, C2, C3, C4, C5, or C6 colon cancer, according to the CRC Inherent Subtype (CRCIS ) system classified as subtype A, B, or C, or any of colon cancers classified as CMS1, CMS2, CMS3, or CMS4 according to the Colorectal Cancer Subtype Consortium (CRCSC) classification system. In some embodiments, the colon cancer has a microsatellite instability (MSI) status of MSI-high or MSI-low. In some embodiments, the individual has previously received treatment (eg, chemotherapy, radiation therapy, surgery, or immunomodulatory therapy). In some embodiments, the individual has not responded to previous therapy (eg, chemotherapy, radiation therapy, surgery, or immunomodulatory therapy).

在一些實施方案中，所述治療或一種或多種治療選擇進一步包含額外的抗癌治療。在一些實施方案中，所述額外的抗癌治療包括小分子抑制劑、抗體、細胞療法或核酸中的一種或多種。在一些實施方案中，所述細胞療法是過繼療法、基於T細胞的療法、基於自然殺傷(NK)細胞的療法、嵌合抗原受體(CAR)-T細胞療法、重組T細胞受體(TCR)T細胞療法或基於樹突狀細胞(DC) 的療法。在一些實施方案中，所述核酸包括雙鏈RNA (dsRNA)、小幹擾RNA (siRNA)或小髮夾RNA(shRNA)。在一些實施方案中，所述額外的抗癌治療包括手術、放射療法、化學療法、抗血管生成療法、抗DNA修復療法、抗炎療法、抗腫瘤劑、化療試劑、生長抑制劑、抗血管生成劑或細胞毒素劑中的一種或多種。In some embodiments, the treatment or one or more treatment options further comprise additional anti-cancer treatments. In some embodiments, the additional anticancer therapy includes one or more of small molecule inhibitors, antibodies, cell therapy, or nucleic acids. In some embodiments, the cell therapy is adoptive therapy, T cell based therapy, natural killer (NK) cell based therapy, chimeric antigen receptor (CAR)-T cell therapy, recombinant T cell receptor (TCR) ) T cell therapy or dendritic cell (DC) based therapy. In some embodiments, the nucleic acid comprises double-stranded RNA (dsRNA), small interfering RNA (siRNA), or small hairpin RNA (shRNA). In some embodiments, the additional anti-cancer therapy includes surgery, radiation therapy, chemotherapy, anti-angiogenic therapy, anti-DNA repair therapy, anti-inflammatory therapy, antineoplastic agents, chemotherapeutic agents, growth inhibitors, anti-angiogenic one or more of cytotoxic or cytotoxic agents.

在一些實施方案中，來自所述個體的樣本包括體液、細胞或組織。在一些實施方案中，來自所述個體的樣本包含腫瘤活檢或迴圈腫瘤細胞。在一些實施方案中，來自所述個體的樣本包含一種或多種核酸。在一些實施方案中，來自所述個體的樣本包含RNA(例如mRNA)、基因組DNA、迴圈腫瘤DNA、遊離DNA或遊離RNA。在一些實施方案中，來自所述個體的樣本包含染色質。在一些實施方案中，來自所述個體的樣本包含一種或多種多肽。在一些實施方案中，所述樣本是福馬林固定石蠟包埋(FFPE)的樣本。在一些實施方案中，所述樣本包含一種或多種核酸(例如DNA、RNA)和/或一種或多種獲自所述個體的FFPE樣本的多肽。在一些實施方案中，所述一種或多種核酸包括mRNA和/或基因組DNA。在一些實施方案中，所述樣本來源於所述個體的結直腸癌組織。In some embodiments, the sample from the individual comprises bodily fluids, cells or tissues. In some embodiments, the sample from the individual comprises a tumor biopsy or circulating tumor cells. In some embodiments, the sample from the individual comprises one or more nucleic acids. In some embodiments, the sample from the individual comprises RNA (eg, mRNA), genomic DNA, circulating tumor DNA, cell-free DNA, or cell-free RNA. In some embodiments, the sample from the individual comprises chromatin. In some embodiments, the sample from the individual comprises one or more polypeptides. In some embodiments, the sample is a formalin-fixed paraffin-embedded (FFPE) sample. In some embodiments, the sample comprises one or more nucleic acids (eg, DNA, RNA) and/or one or more polypeptides obtained from the FFPE sample of the individual. In some embodiments, the one or more nucleic acids include mRNA and/or genomic DNA. In some embodiments, the sample is derived from colorectal cancer tissue from the individual.

在一些實施方案中，在異常性(例如，突變或表達或活性或修飾)分析之前，選擇性增濃樣本的某些類型的多肽(例如，由一個或多個藥物敏感性基因和/或一個或多個耐藥基因編碼的多肽或其部分)。在一些實施方案中，所述選擇性增濃包含：(a)將誘餌（bait）與樣本結合，從而使誘餌與樣本中的一種或多種多肽結合並產生誘餌-多肽複合物；和(b)單離誘餌-多肽複合物以產生增濃的樣本。在一些實施方案中，所述誘餌包含捕獲多肽分子，所述捕獲多肽分子被配置為結合由一個或多個選自下組的藥物敏感性基因編碼的多肽(或其部分)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或由一個或多個選自下組的耐藥基因編碼的多肽(或其部分)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。在一些實施方案中，所述誘餌包含捕獲多肽分子，所述捕獲多肽分子被配置為結合由一個或多個選自下組的藥物敏感性基因編碼的多肽(或其部分)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或由一個或多個選自下組的耐藥基因編碼的多肽(或其部分)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述誘餌包含捕獲多肽分子，所述捕獲多肽分子被配置為結合由一個或多個選自下組的藥物敏感性基因編碼的多肽(或其部分)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或由一個或多個選自下組的耐藥基因編碼的多肽(或其部分)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述誘餌包含捕獲多肽分子，所述捕獲多肽分子被配置為結合由一個或多個選自下組的藥物敏感性基因編碼的多肽(或其部分)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或由一個或多個選自下組的耐藥基因編碼的多肽(或其部分)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，所述誘餌包含捕獲多肽分子，所述捕獲多肽分子被配置為結合由一個或多個選自下組的藥物敏感性基因編碼的多肽(或其部分)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或由一個或多個選自下組的耐藥基因編碼的多肽(或其部分)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。在一些實施方案中，所述誘餌包含捕獲多肽分子，所述捕獲多肽分子被配置為結合由一個或多個選自下組的藥物敏感性基因編碼的多肽(或其部分)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或由一個或多個選自下組的耐藥基因編碼的多肽(或其部分)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。在一些實施方案中，所述捕獲多肽分子是多肽。在一些實施方案中，所述捕獲多肽分子是抗體或抗體片段。在一些實施方案中，所述誘餌與親和試劑或偵測試劑綴合。在一些實施方案中，所述親和試劑是生物素。在一些實施方案中，所述偵測試劑是螢光標記物。在一些實施方案中，所述方法還包含對增濃樣本中的一種或多種多肽進行蛋白質定序或質譜分析。In some embodiments, the sample is selectively enriched for certain types of polypeptides (e.g., caused by one or more drug susceptibility genes and/or a or polypeptides encoded by multiple drug resistance genes or parts thereof). In some embodiments, the selective enrichment comprises: (a) combining a bait with a sample, so that the bait binds to one or more polypeptides in the sample and generates a bait-polypeptide complex; and (b) The bait-polypeptide complex is isolated to produce an enriched sample. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a polypeptide (or portion thereof) encoded by one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA , DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or polypeptides (or parts thereof) encoded by one or more resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2 G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a polypeptide (or portion thereof) encoded by one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA , DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or polypeptides (or parts thereof) encoded by one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a polypeptide (or portion thereof) encoded by one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or a polypeptide (or part thereof) encoded by one or more resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a polypeptide (or portion thereof) encoded by one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or a polypeptide (or part thereof) encoded by one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a polypeptide (or portion thereof) encoded by one or more drug susceptibility genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or are selected from one or more of the following Polypeptides (or parts thereof) encoded by drug-resistant genes of the group: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a polypeptide (or portion thereof) encoded by one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, Kiaa1109, MGA, Dok5, STK11, NFE2L1, ENC1, HDAC2, Gucy2D, Adamts2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, CSNK1G1, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11 , WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B , and/or a polypeptide (or part thereof) encoded by one or more drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G 2. DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1 . In some embodiments, the capture polypeptide molecule is a polypeptide. In some embodiments, the capture polypeptide molecule is an antibody or antibody fragment. In some embodiments, the bait is conjugated to an affinity or detection reagent. In some embodiments, the affinity reagent is biotin. In some embodiments, the detection reagent is a fluorescent marker. In some embodiments, the method further comprises protein sequencing or mass spectrometry analysis of the one or more polypeptides in the enriched sample.

在一些實施方案中，在異常性(例如，突變或表達或活性)分析之前，選擇性增濃樣本的某些類型的多肽(例如，包含或由一個或多個藥物敏感性基因和/或一個或多個耐藥基因編碼的核酸)。在一些實施方案中，所述選擇性增濃包含：(a)將誘餌與所述樣本結合，從而使所述誘餌與樣本中的一種或多種核酸雜交並產生核酸雜交體；(b)單離核酸雜交體以產生增濃樣本。在一些實施方案中，所述誘餌包含捕獲核酸分子，所述捕獲核酸分子被配置為與一個或多個選自下組的藥物敏感性基因(或其編碼的RNA)雜交：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因(或其編碼的RNA)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。在一些實施方案中，所述誘餌包含捕獲核酸分子，所述捕獲核酸分子被配置為雜交一個或多個選自下組的藥物敏感性基因(或其編碼的RNA)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因(或其編碼的RNA)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，是誘餌包含捕獲核酸分子，所述捕獲核酸分子被配置為雜交一個或多個選自下組的藥物敏感性基因(或其編碼的RNA)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因(或其編碼的RNA)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述誘餌包含捕獲核酸分子，所述捕獲核酸分子被配置為與一個或多個選自下組的藥物敏感性基因(或其編碼的RNA)雜交：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一個或多個選自下組的耐藥基因(或其編碼的RNA)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，所述誘餌包含捕獲核酸分子，所述捕獲核酸分子被配置為雜交一個或多個選自下組的藥物敏感性基因(或其編碼的RNA)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因(或其編碼的RNA)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。在一些實施方案中，所述誘餌包含捕獲核酸分子，所述捕獲核酸分子被配置為雜交一個或多個選自下組的藥物敏感性基因(或其編碼的RNA)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因(或其編碼的RNA)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。在一些實施方案中，所述捕獲核酸分子包含約10至約30個核苷酸、約50至約1000個核苷酸、約100至約500個核苷酸、約100至約300個核苷酸或約100至200個核苷酸。在一些實施方案中，所述誘餌與親和試劑或偵測試劑綴合。在一些實施方案中，所述親和試劑是抗體、抗體片段或生物素，或者其中偵測試劑是螢光標記物。在一些實施方案中，所述捕獲核酸分子包含DNA、RNA或混合的DNA/RNA分子。在一些實施方案中，所述選擇性增濃包含使用聚合酶鏈式反應(PCR)擴增樣本中的一種或多種核酸以產生增濃的樣本。在一些實施方案中，所述方法進一步包含對增濃樣本中的一種或多種核酸分子或其相關部分(例如已知含有突變的核酸片段)進行定序。In some embodiments, the sample is selectively enriched for certain types of polypeptides (e.g., comprising or consisting of one or more drug sensitivity genes and/or a or nucleic acids encoding multiple drug resistance genes). In some embodiments, the selective enrichment comprises: (a) binding a bait to the sample, whereby the bait hybridizes to one or more nucleic acids in the sample and generates a nucleic acid hybrid; (b) isolating Nucleic acid hybrids to generate enriched samples. In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to one or more drug sensitivity genes (or RNA encoded thereof) selected from the group consisting of PTEN, CAB39, RIF1 , STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2 , ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2 , GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1 , DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12 , CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2 , NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1 , HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP 2. AKAP12 , LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DPM, DPM, DPM 2. PTPN11, WNT7B, OTOA, DTX1 , ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C , RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes (or RNAs thereof) selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2 , TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR , NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1 , MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16 , ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3 , NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B , BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH , CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12 B , EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK , DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to one or more drug susceptibility genes (or RNAs thereof) selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, HPRT1, DNAH11, DPM2, DPM2, DPM2 , PTPN11, Wnt7b, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes (or RNAs thereof) selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to one or more drug sensitivity genes (or RNAs thereof) selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN , PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE , and FANCM, and/or one or more drug resistance genes (or RNAs thereof) selected from the group consisting of RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R , RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to one or more drug sensitivity genes (or RNA encoded thereof) selected from the group consisting of PTEN, CAB39, RIF1 , STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2 , ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2 , GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1 , DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51 , FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more drug resistance genes (or RNAs thereof) selected from the group consisting of: PARP1, MAPK1, TCF7L2 , MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL , GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2 , DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B , E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA , HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to one or more drug sensitivity genes (or RNAs thereof) selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or one or more resistance selected from the following group Drug genes (or their encoded RNA): PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to one or more drug sensitivity genes (or RNAs thereof) selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, Kiaa1109, MGA, Dok5, STK11, NFE2L1, ENC1, HDAC2, Gucy2D, Adamts2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, CSNK1G1, DSP, RP, RP, RP, RP S6KA5, BMP8B, Mapk14, PARP2, PTEN, PTEN, PTEN, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B , OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and /or one or more drug resistance genes (or their encoded RNA) selected from the following group: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CT NNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1. In some embodiments, the capture nucleic acid molecule comprises about 10 to about 30 nucleotides, about 50 to about 1000 nucleotides, about 100 to about 500 nucleotides, about 100 to about 300 nucleosides acid or about 100 to 200 nucleotides. In some embodiments, the bait is conjugated to an affinity or detection reagent. In some embodiments, the affinity reagent is an antibody, antibody fragment, or biotin, or wherein the detection reagent is a fluorescent label. In some embodiments, the capture nucleic acid molecules comprise DNA, RNA, or mixed DNA/RNA molecules. In some embodiments, the selective enrichment comprises amplifying one or more nucleic acids in the sample using polymerase chain reaction (PCR) to produce an enriched sample. In some embodiments, the method further comprises sequencing one or more nucleic acid molecules or related portions thereof (eg, nucleic acid fragments known to contain mutations) in the enriched sample.

在一些實施方案中，提供了多種捕獲核酸分子(或多種誘餌，其中每個誘餌包含捕獲核酸分子)，其被配置為雜交選自下組的多種藥物敏感性基因(或其編碼的RNA)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或選自下組的多個耐藥基因(或其編碼的RNA)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。在一些實施方案中，提供了多種捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多種藥物敏感性基因(或其編碼的RNA)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或選自下組的多個耐藥基因(或其編碼的RNA)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，提供了多種捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多種藥物敏感性基因(或其編碼的RNA)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或選自下組的多個耐藥基因(或其編碼的RNA)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，提供了多種捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多種藥物敏感性基因(或其編碼的RNA)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或選自下組的多個耐藥基因(或其編碼的RNA)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，提供了多種捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多種藥物敏感性基因(或其編碼的RNA)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或選自下組的多個耐藥基因(或其編碼的RNA)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。在一些實施方案中，提供了多種捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多個藥物敏感性基因(或其編碼的RNA)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或選自下組的多個耐藥基因(或其編碼的RNA)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多個藥物敏感性基因(或其編碼的RNA)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或選自下組的多個耐藥基因(或其編碼的RNA)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多個藥物敏感性基因(或其編碼的RNA)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或選自下組的多個耐藥基因(或其編碼的RNA)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多個藥物敏感性基因(或其編碼的RNA)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或選自下組的多個耐藥基因(或其編碼的RNA)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多個藥物敏感性基因(或其編碼的RNA)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或選自下組的多個耐藥基因(或其編碼的RNA)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多個藥物敏感性基因(或其編碼的RNA)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或選自下組的多個耐藥基因(或其編碼的RNA)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或多個誘餌，其中每個誘餌包含捕獲核酸分子)，所述捕獲核酸分子被配置為雜交選自下組的多個藥物敏感性基因(或其編碼的RNA)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或選自下組的多個耐藥基因(或其編碼的RNA)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。在一些實施方案中，所述捕獲核酸分子包含約10至約30個核苷酸、約50至約1000個核苷酸、約100至約500個核苷酸、約100至約300個核苷酸或約100至200個核苷酸。在一些實施方案中，所述誘餌與親和試劑或偵測試劑綴合。在一些實施方案中，所述親和試劑是抗體、抗體片段或生物素，或者其中所述偵測試劑是螢光標記物。在一些實施方案中，所述捕獲核酸分子包含DNA、RNA或混合的DNA/RNA分子。在一些實施方案中，選擇性增濃包含使用PCR擴增樣本中的一種或多種核酸以產生增濃的樣本。在一些實施方案中，所述方法進一步包含對增濃樣本中的一種或多種核酸分子或其相關部分(例如已知含有突變的核酸片段)進行定序。 In some embodiments, a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitivity genes (or RNAs thereof) selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1 , PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11 , WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2 G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. In some embodiments, a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitivity genes selected from the group consisting of (or a plurality of baits) is provided. encoded RNA): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN , DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X , AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A , YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B , WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4 , KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5 , STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN 、MRGBP , HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNA H11 , DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A , RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of RPTOR, TP53 , ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1 , EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitivity genes selected from the group consisting of (or a plurality of baits) is provided. Encoding RNAs): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2 , ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4 , CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1 , and EIF4B. In some embodiments, a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitivity genes selected from the group consisting of (or a plurality of baits) is provided. encoded RNA): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN , DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X , AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A , YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B , WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or multiple drug resistance genes (or their encoded RNA): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1 , USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1 , CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2 , BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3 , ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. In some embodiments, a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitivity genes selected from the group consisting of (or a plurality of baits) is provided. encoded RNA): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2 , MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or Or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK , IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1 , MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. In some embodiments, a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitivity genes selected from the group consisting of (or its encoded RNA): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PE G3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, Dok4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, Dock1, Znf469, PLA2G12B, EGFR, WDFY4, Gal3st4, Kiaa12, Kiaa12 17. Mapk3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of capture nucleic acid molecules selected from the group consisting of Drug sensitivity genes (or their encoded RNAs): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or multiple drug resistance genes selected from the group below (or Encoding RNA): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1 , RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC , RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5 , SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA , E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2 , MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B , DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2 , CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2 , COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of capture nucleic acid molecules selected from the group consisting of Drug sensitivity genes (or their encoded RNAs): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI , DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4 , ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1 、ACTB , TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF5 68. FGF23 , PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG , DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or multiple drug resistance genes selected from the group below (or Encoding RNAs): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1 , MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of capture nucleic acid molecules selected from the group consisting of Drug sensitivity genes (or their encoded RNAs): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1 , GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of RPTOR, TP53, ID1 , MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR , SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of capture nucleic acid molecules selected from the group consisting of Drug sensitivity genes (or their encoded RNAs): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2 , FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A , CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE , ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS , HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or a plurality selected from the group Drug resistance genes (or their encoded RNA): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2 , PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1 , BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1 , CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1 , PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of capture nucleic acid molecules selected from the group consisting of Drug sensitivity genes (or their encoded RNA): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C , RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4 , NIPBL, and ATRX, and/or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1 , CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2 , DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or a plurality of baits, wherein each bait comprises a capture nucleic acid molecule) configured to hybridize to a plurality of capture nucleic acid molecules selected from the group consisting of Drug sensitivity genes (or their encoded RNAs): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A , TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2 , RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D , GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP , MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN 1A, SMAD7 , ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28 , LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or multiple drug resistance genes (or RNAs thereof) selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9 , CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7 , STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5 , CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1 , MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3 BFB , NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18 , DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1. In some embodiments, the capture nucleic acid molecule comprises about 10 to about 30 nucleotides, about 50 to about 1000 nucleotides, about 100 to about 500 nucleotides, about 100 to about 300 nucleosides acid or about 100 to 200 nucleotides. In some embodiments, the bait is conjugated to an affinity or detection reagent. In some embodiments, the affinity reagent is an antibody, antibody fragment, or biotin, or wherein the detection reagent is a fluorescent label. In some embodiments, the capture nucleic acid molecules comprise DNA, RNA, or mixed DNA/RNA molecules. In some embodiments, selectively enriching comprises using PCR to amplify one or more nucleic acids in the sample to produce an enriched sample. In some embodiments, the method further comprises sequencing one or more nucleic acid molecules or related portions thereof (eg, nucleic acid fragments known to contain mutations) in the enriched sample.

在一些實施方案中，本文提供了一種系統，其包含：被配置為存儲一個或多個程式指令的記憶體；和一個或多個被配置為執行所述一個或多個程式指令的處理器，其中所述一個或多個程式指令在由一個或多個處理器執行時被配置為：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體(例如人)獲得的樣本；(b)分析所述多個序列讀長以確定是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a system comprising: a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions, wherein the one or more program instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or a plurality of nucleic acids or polypeptides derived from a sample obtained from an individual (e.g., a human) with colorectal cancer; (b) analyzing the plurality of sequence reads to determine whether there is one or more drug sensitivities selected from the group consisting of One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS 2. ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C , CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more selected from the following group One or more resistance abnormalities (such as resistance mutations) in the resistance genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1 , EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R , NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1 , GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1 , EPHA5, BCAR1, CKS1B, EIF4A1, Plec, Crebbp, RELA, E2F3, ITIH6, BRPF3, Anapc7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, FGF19, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E 2. TNFRSF17, CUL9, CDC25A, KMT2D , FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR , PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A , FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET 、SKP2 , BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A , CHEK1, PKMYT1, SIDT2, and GAB1; and (c) detecting, based on the analysis, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1 , PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11 , WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, One or more drug resistance abnormalities (such as drug resistance mutations) in EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes selected from the group below : PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28 , PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2 , AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL , ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6 D USP5 , NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1 , DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34 , PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNBIP1, SCN3A, DOCK6, ROCK2, COMP, AR ID2 , RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供了一種系統，包含：被配置為存儲一個或多個程式指令的記憶體；和一個或多個被配置為執行所述一個或多個程式指令的處理器，其中所述一個或多個程式指令在由一個或多個處理器執行時被配置為：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體(例如人)獲得的樣本；(b)分析所述多個序列讀長以確定是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a system comprising: a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions, wherein The one or more program instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more A plurality of nucleic acids or polypeptides is derived from a sample obtained from an individual (e.g., a human) with colorectal cancer; (b) analyzing the plurality of sequence reads to determine whether there is one or more drug sensitivity genes selected from the group consisting of One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B , TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10 , GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15 , SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34 , E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213 , EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4 , ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2 , ANAPC7 , DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDK N1A , ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C , WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more selected from the following group One or more resistance abnormalities (eg, resistance mutations) in resistance genes: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B; and (c) detecting one or more selections based on the analysis One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in drug sensitivity genes from the following group: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7 , CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1 , DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM , PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13 , TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A , TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2 , CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, M APK14 , PARP2, HSP90AB1, CKS2, Anapc7, DIDO1, ACTB, TP53bp1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, Magi2, Magi2, Magi2 , PTP4A3, PARP14, AXL, GRB2, CR1, Foxo1 , TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR A One or more drug resistance abnormalities (such as drug resistance mutations) in multiple drug resistance genes selected from the following group: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供了一種系統，包含：被配置為存儲一個或多個程式指令的記憶體；和被配置為執行一個或多個程式指令的一個或多個處理器，其中當由所述一個或多個處理器執行時，所述一個或多個程式指令被配置為：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體(例如人)獲得的樣本；(b)分析所述多個序列讀長以確定是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a system comprising: a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions, wherein when the When executed by the one or more processors, the one or more program instructions are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more or a plurality of nucleic acids or polypeptides derived from a sample obtained from an individual (e.g., a human) with colorectal cancer; (b) analyzing the plurality of sequence reads to determine whether there is one or more drug sensitivities selected from the group consisting of One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more genes: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or one or more resistance genes selected from the following group Drug abnormalities (eg, resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1 , AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B; and (c) detecting one or more drug sensitivity genes selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations): GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, One or more drug resistance abnormalities in PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or one or more drug resistance genes selected from the group below (e.g. resistance mutations): RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1 , MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供了一種系統，包含：被配置為存儲一個或多個程式指令的記憶體；被配置為執行所述一個或多個程式指令的一個或多個處理器，其中所述一個或多個程式指令在由一個或多個處理器執行時被配置為：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體(例如人)獲得的樣本；(b)分析所述多個序列讀長以確定是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1、和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19；和(c)基於所述分析，偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，本文提供一種系統，包含：被配置為存儲一個或多個程式指令的記憶體；以及被配置為執行所述一個或多個程式指令的一個或多個處理器，其中所述一個或多個程式指令在由一個或多個處理器執行時被配置為：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體(例如人)獲得的樣本；(b)分析所述多個序列讀長以確定是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a system comprising: memory configured to store one or more program instructions; one or more processors configured to execute the one or more program instructions, wherein the The one or more program instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more The nucleic acid or polypeptide is derived from a sample obtained from an individual (e.g., a human) with colorectal cancer; (b) analyzing the plurality of sequence reads to determine whether there is one or more drug sensitivity genes selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more One or more resistance abnormalities (eg, resistance mutations) in resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC , RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF , WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1 , CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A , FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1 , SIDT2, and FGF19; and (c) based on said analysis, detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39 , RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2 , DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B , TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2 , WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A , RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more drug resistance abnormalities (such as resistance to drug mutation): PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. In some embodiments, provided herein is a system comprising: a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions, wherein the The one or more program instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more The nucleic acid or polypeptide is derived from a sample obtained from an individual (e.g., a human) with colorectal cancer; (b) analyzing the plurality of sequence reads to determine whether there is one or more drug sensitivity genes selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations): ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, One or more resistance abnormalities (eg, resistance mutations) in GSK3B, SCAF4, NIPBL, and ATRX, and/or one or more resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A , ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF , SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1; and (c) detecting one or more selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in the drug sensitivity genes: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, One or more drug resistance abnormalities (such as drug resistance mutations) in TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or one or more drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1 , MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2 , PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供一種系統，包含：被配置為存儲一個或多個程式指令的記憶體；以及被配置為執行所述一個或多個程式指令的一個或多個處理器，其中所述一個或多個程式指令在由一個或多個處理器執行時被配置為：(a)獲得一種或多種核酸(例如DNA或RNA)或肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體(例如人)獲得的樣本；(b)分析所述多個序列讀長以確定是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a system comprising: a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions, wherein the The one or more program instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or peptides, wherein the one or more The nucleic acid or polypeptide is derived from a sample obtained from an individual (e.g., a human) with colorectal cancer; (b) analyzing the plurality of sequence reads to determine whether there is one or more drug sensitivity genes selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX 3. NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G 2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, One or more drug resistance abnormalities (such as drug resistance mutations) in PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or one or more drug resistance genes selected from the group below : RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C , ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA , PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556 , CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR , WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1 , FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1; and (c) detecting one or more drug sensitivity genes selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations): ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX 3. NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G 2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, One or more drug resistance abnormalities (such as drug resistance mutations) in PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or one or more drug resistance genes selected from the group below : RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C , ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA , PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556 , CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR , WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1 , FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供了一種非暫時性電腦可讀存儲介體，包含一個或多個可由一個或多個電腦處理器執行以運行方法的程式，其中所述方法包含：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長中是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a non-transitory computer-readable storage medium comprising one or more programs executable by one or more computer processors to perform a method, wherein the method comprises: (a) obtaining a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual with colorectal cancer; (b) analyzing the plurality of Whether there are one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group in the sequence read length: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, Foxo3, NAV2, RAC3, TSPAN1, RPS6KA2, Chek2, CSNK1E, YWHAB, ID4, AdamTS5, MXD4, ANK2, NOG, Kiaa1109, Dok5, ENC1, Gucy2D, ADAMTS22 , DLEC1, HSPG2, Trib3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1 , MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53 , CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2 , MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12 , YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1 , KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1 , MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R 1B, BMP7 , STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2 PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, Chuk, Dok4, POLRMT, PLCE1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CC NE1, Dock1, Znf469, PLA2G12B, EGFR , WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B , FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1; and (c) detecting one or more drug sensitivity selected from the group based on the analysis One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS 2. ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C , CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more selected from the following group One or more resistance abnormalities (such as resistance mutations) in the resistance genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1 , EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R , NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1 , GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1 , EPHA5, BCAR1, CKS1B, EIF4A1, Plec, Crebbp, RELA, E2F3, ITIH6, BRPF3, Anapc7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, FGF19, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E, EIF4E 2. TNFRSF17, CUL9, CDC25A, KMT2D , FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR , PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A , FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET 、SKP2 , BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A , CHEK1, PKMYT1, SIDT2, and GAB1. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供一種非暫時性電腦可讀存儲介體，其包含一個或多個可由一個或多個電腦處理器執行以運行方法的程式，其中所述方法包含：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長中是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a non-transitory computer-readable storage medium comprising one or more programs executable by one or more computer processors to perform a method, wherein the method comprises: (a) obtaining a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual with colorectal cancer; (b) analyzing the plurality of Whether there are one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group in the sequence read length: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, Foxo3, NAV2, RAC3, TSPAN1, RPS6KA2, Chek2, CSNK1E, YWHAB, ID4, AdamTS5, MXD4, ANK2, NOG, Kiaa1109, Dok5, ENC1, Gucy2D, ADAMTS22 , DLEC1, HSPG2, Trib3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1 , MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4 , CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1 , and EIF4B; and (c) detecting, based on said analysis, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, HPRT1, DNAH11, DPM2, DPM2, DPM2 , PTPN11, Wnt7b, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, One or more drug resistance abnormalities (such as drug resistance mutations) in RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1 , MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR , SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供一種非暫時性電腦可讀存儲介體，其包含一個或多個可由一個或多個電腦處理器執行以運行方法的程式，其中所述方法包含：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長中是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a non-transitory computer-readable storage medium comprising one or more programs executable by one or more computer processors to perform a method, wherein the method comprises: (a) obtaining a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual with colorectal cancer; (b) analyzing the plurality of Whether there are one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group in the sequence read length: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or One or more resistance abnormalities (eg, resistance mutations) in one or more resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R , RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B; and (c) based on the The assay detects one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and/or one or One or more drug resistance abnormalities (such as drug resistance mutations) in multiple drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR , MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供一種非暫時性電腦可讀存儲介體，其包含一個或多個可由一個或多個電腦處理器執行以運行方法的程式，其中所述方法包含：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長中是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。在一些實施方案中，本文提供了一種非暫時性電腦可讀存儲介體，其包含一個或多個可由一個或多個電腦處理器執行以運行方法的程式，其中所述方法包含：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長中是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a non-transitory computer-readable storage medium comprising one or more programs executable by one or more computer processors to perform a method, wherein the method comprises: (a) obtaining a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual with colorectal cancer; (b) analyzing the plurality of Whether there are one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group in the sequence read length: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8 , HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11 , SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2 , RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4 , VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1 , CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19; and (c) detecting one or more drug sensitivity genes selected from the group consisting of One or more drug sensitivity abnormalities (such as drug sensitivity mutations): PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more One or more resistance abnormalities (eg, resistance mutations) in resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC , RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF , WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1 , CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A , FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1 , SIDT2, and FGF19. In some embodiments, provided herein is a non-transitory computer-readable storage medium comprising one or more programs executable by one or more computer processors to perform a method, wherein the method comprises: (a) obtaining a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual with colorectal cancer; (b) analyzing the plurality of sequence reads Whether there are one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group in the sequence read length: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1 , ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7 , HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or one or more of one or more drug resistance genes selected from the following group Drug resistance abnormalities (such as drug resistance mutations): PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1; and (c) detecting, based on said analysis, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1 , FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2 , CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or one or more drug resistance selected from the group One or more resistance abnormalities (such as resistance mutations) in genes: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，本文提供一種非暫時性電腦可讀存儲介體，其包含一個或多個可由一個或多個電腦處理器執行以運行方法的程式，其中所述方法包含：(a)獲得一種或多種核酸(例如DNA或RNA)或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長中是否存在一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。在一些實施方案中，所述序列讀長由基因組定序(DNA-SEQ)獲得。在一些實施方案中，所述序列讀長由轉錄組定序(RNA-SEQ)獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。In some embodiments, provided herein is a non-transitory computer-readable storage medium comprising one or more programs executable by one or more computer processors to perform a method, wherein the method comprises: (a) obtaining a plurality of sequence reads of one or more nucleic acids (e.g., DNA or RNA) or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual with colorectal cancer; (b) analyzing the plurality of Whether there are one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the following group in the sequence read length: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, Dok5, STK11, NFE2L1, ENC1, HDAC2, Gucy2D, AdamTS2, DLEC1, HSPG2, Trib3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2,, PARP2,, PARP2, PARP2,, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C , MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or one or more selected from One or more resistance abnormalities (eg, resistance mutations) in the following groups of resistance genes: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2 , CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1 , IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4 , PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN , CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNB IP1, GNA11 , SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1; and (c) Based on the analysis, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) are detected in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, Dok5, STK11, NFE2L1, ENC1, HDAC2, Gucy2D, AdamTS2, DLEC1, HSPG2, Trib3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2,, PARP2,, PARP2, PARP2,, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C , MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or one or more selected from One or more resistance abnormalities (eg, resistance mutations) in the following groups of resistance genes: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2 , CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1 , IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4 , PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN , CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNB IP1, GNA11 , SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1. In some embodiments, the sequence reads are obtained by genome sequencing (DNA-SEQ). In some embodiments, the sequence reads are obtained by transcriptome sequencing (RNA-SEQ). In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry).

在一些實施方案中，所述一種或多種突變包含一種或多種核苷酸的插入、缺失或取代，染色體重排，啟動子的改變，基因融合或拷貝數改變。在一些實施方案中，所述一種或多種突變導致由藥物敏感性基因或耐藥基因編碼的多肽中的一個或多個胺基酸殘基的一種或多種插入、缺失或取代。In some embodiments, the one or more mutations comprise insertions, deletions or substitutions of one or more nucleotides, chromosomal rearrangements, changes in promoters, gene fusions or copy number changes. In some embodiments, the one or more mutations result in one or more insertions, deletions or substitutions of one or more amino acid residues in the polypeptide encoded by the drug sensitivity gene or drug resistance gene.

在一些實施方案中，所述多個序列讀長藉由定序、全外顯子組定序、RNA定序、全基因組定序、基因靶向定序或下一代定序獲得。在一些實施方案中，所述序列讀長由蛋白質定序(例如質譜)獲得。在一些實施方案中，對整個基因或基因產物(例如RNA、多肽)進行定序。在一些實施方案中，對基因或基因產物(例如RNA、多肽)的相關部分（例如已知含有突變或修飾的核酸或多肽片段）進行定序。In some embodiments, the plurality of sequence reads are obtained by sequencing, whole exome sequencing, RNA sequencing, whole genome sequencing, gene targeted sequencing, or next generation sequencing. In some embodiments, the sequence reads are obtained from protein sequencing (eg, mass spectrometry). In some embodiments, an entire gene or gene product (eg, RNA, polypeptide) is sequenced. In some embodiments, relevant portions (eg, fragments of nucleic acids or polypeptides known to contain mutations or modifications) of genes or gene products (eg, RNA, polypeptides) are sequenced.

在一些實施方案中，本文提供了用於治療結直腸癌的方法中的DNA損傷劑(例如PARPi或ATRi)，其中所述方法包含向患有結直腸癌的個體(例如人)投予DNA損傷劑，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B。在一些實施方案中，本文提供了用於治療結直腸癌的方法中的DNA損傷劑(例如PARPi或ATRi)，其中所述方法包含將所述DNA損傷劑投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B、以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating colorectal cancer, wherein the method comprises administering a DNA damaging agent to an individual (e.g., a human) having colorectal cancer An agent wherein one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1 are detected in a sample obtained from said individual , STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2 , ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2 , GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1 , DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12 , CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2 , NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1 , HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP 2. AKAP12 , LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DPM, DPM, DPM 2. PTPN11, WNT7B, OTOA, DTX1 , ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C , RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B. In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual having colorectal cancer (e.g. human), wherein one or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B , OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1 , TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A , VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1 , SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6 , KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7 , NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MyH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, Foxg1, Arid1a, TSC1, Smad2, CCDC, CCDCC1, Smad2, CCDCC1 168, MyH2, MDM2, Dusp5, NCK1, APC , VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4 , PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1 , CCNE1, Dock1, Znf469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, Kiaa1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A,, SCN3A, SCN3A, Dock6, ROCK2, COMP, Arid2, RHOA, JPH3 , TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, and drug sensitivity abnormalities (such as drug sensitivity mutations ) and drug resistance abnormalities (such as drug resistance mutations) were higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了用於治療結直腸癌的方法中的DNA損傷劑(例如PARPi或ATRi)，其中所述方法包含將所述DNA損傷劑給予患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B、以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual having colorectal cancer (e.g., Human), wherein one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA , DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, One or more drug resistance abnormalities (such as drug resistance mutations) in RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance genes selected from the group: RPTOR, TP53, ID1 , MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR , SRC, PIK3CA, CHD2, PARP1, and EIF4B, and the combined score of drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) is higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了用於治療結直腸癌的方法中的DNA損傷劑(例如PARPi或ATRi)，其中所述方法包含將所述DNA損傷劑投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM。在一些實施方案中，本文提供了用於治療結直腸癌的方法中的DNA損傷劑(例如PARPi或ATRi)，其中所述方法包含將所述DNA損傷劑投予於患有結直腸癌的個體(例如人) , 其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM、以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual having colorectal cancer (e.g. a human), wherein one or more drug sensitivity aberrations (e.g. drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM. In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual having colorectal cancer (eg human), wherein one or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, One or more drug resistance abnormalities (such as drug resistance mutations) in BAZ1A, ATM, YWHAE, and FANCM, and one or more drug resistance genes selected from the group consisting of: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4 , CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1 , and EIF4B, and wherein the composite score of drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) is higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了用於治療結直腸癌的方法中的PARP抑制劑，其中所述方法包含將所述PARP抑制劑投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1。在一些實施方案中，本文提供了用於治療結直腸癌的方法中的PARP抑制劑，其中所述方法包含將PARP抑制劑投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX。在一些實施方案中，本文提供了用於治療結直腸癌的方法中的PARP抑制劑，其中所述方法包含將PARP抑制劑投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1、以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，本文提供了用於治療結直腸癌的方法中的PARP抑制劑，其中所述方法包含將PARP抑制劑投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX、以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are PARP inhibitors for use in a method of treating colorectal cancer, wherein the method comprises administering the PARP inhibitor to an individual (e.g., a human) having colorectal cancer, wherein One or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1. In some embodiments, provided herein are PARP inhibitors for use in a method of treating colorectal cancer, wherein the method comprises administering a PARP inhibitor to an individual (e.g., a human) having colorectal cancer, wherein the One or more drug sensitivity abnormalities (eg drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX. In some embodiments, provided herein are PARP inhibitors for use in a method of treating colorectal cancer, wherein the method comprises administering a PARP inhibitor to an individual (e.g., a human) having colorectal cancer, wherein the One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, One or more drug resistance abnormalities (such as drug resistance mutations) in RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2 , MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL , GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2 , DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B , E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA , HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, and wherein drug sensitivity abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations ) with a composite score higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, provided herein are PARP inhibitors for use in a method of treating colorectal cancer, wherein the method comprises administering a PARP inhibitor to an individual (e.g., a human) having colorectal cancer, wherein the One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and one or more drug resistance genes selected from the following group or Multiple resistance abnormalities (eg, resistance mutations): PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2 , KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1 , and RBL1, and the composite score of abnormal drug sensitivity (such as drug sensitivity mutation) and drug resistance abnormality (such as drug resistance mutation) is higher than the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了用於治療結直腸癌的方法中的ATRi，其中所述方法包含將所述ATRi投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B。在一些實施方案中，本文提供了用於治療結直腸癌的方法中的ATRi，其中所述方法包含將ATRi投予於患有結直腸癌的個體(例如人)，其中在從所述個體獲得的樣本中偵測到一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B、以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常(例如耐藥突變)：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，並且其中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is an ATRi for use in a method of treating colorectal cancer, wherein said method comprises administering said ATRi to an individual (e.g., a human) having colorectal cancer, wherein said ATRi is obtained from said One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP9 0AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B. In some embodiments, provided herein is an ATRi for use in a method of treating colorectal cancer, wherein the method comprises administering the ATRi to an individual (e.g., a human) having colorectal cancer, wherein One or more drug sensitivity abnormalities (such as drug sensitivity mutations) were detected in one or more drug sensitivity genes selected from the following group: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, Dok5, STK11, NFE2L1, ENC1, HDAC2, Gucy2D, AdamTS2, DLEC1, HSPG2, Trib3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2,, PARP2,, PARP2, PARP2,, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C , MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and one or more selected from the group One or more resistance abnormalities (such as resistance mutations) in the resistance genes: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2 , MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG , CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2 , PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1 , USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11 , SCN3A , DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, and drug sensitivity abnormalities (such as drug susceptibility mutations) and drug resistance abnormalities (such as drug resistance mutations) were above the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

應當理解，本文描述的各種實施方案的一個、一些或所有特性可以組合以形成本發明的其他實施方案。本發明的這些和其他態樣對於熟習此項技術者將變得顯而易見。本發明的這些和其他實施方案藉由以下詳細描述進一步闡述。It should be understood that one, some or all features of the various embodiments described herein may be combined to form other embodiments of the invention. These and other aspects of the invention will become apparent to those skilled in the art. These and other embodiments of the invention are further illustrated by the following detailed description.

本申請至少部分基於某些生物標記的發現及其與對DNA損傷劑(例如PARP抑制劑或ATRi)的治療的藥物敏感性或藥物抗性的關聯。具體而言，使用具有自主智慧財產權的高通量篩選平臺，發明人已經鑒定了一組基因(稱為“藥物敏感性基因”)，當它們在結直腸癌細胞中發生突變(例如失活)時，使結直腸癌細胞（與不具有此類突變的結直腸癌細胞相比）對使用DNA損傷劑(例如PARP抑制劑或ATRi)的治療更敏感。發明人還鑒定了一組基因(稱為“耐藥基因”)，當它們在結直腸癌細胞中發生突變(例如失活)時，使結直腸癌細胞（與不具有此類突變的結直腸癌細胞相比）對使用DNA損傷劑(例如PARP抑制劑或ATRi)的治療更具耐藥性。這些基因中的異常(例如，突變、表達異常、活性異常和/或異常修飾(例如翻譯後修飾))可以是用於用DNA損傷劑(例如PARP抑制劑或ATRi)治療(或不治療)患有結直腸癌的個體的有用生物標記。例如，與健康個體相比，在本文描述的藥物敏感性基因中攜帶突變(例如失活)和/或藥物敏感性基因表達(例如mRNA或蛋白質)減少或缺失的患者，和/或與健康個體相比，藥物敏感性基因的活性(例如，RNA或蛋白質活性，例如由於表觀遺傳或翻譯後修飾)降低或消失的患者，特別適用於與使用相應的抗癌藥物進行治療。The present application is based at least in part on the discovery of certain biomarkers and their association with drug sensitivity or drug resistance to treatment with DNA damaging agents such as PARP inhibitors or ATRi. Specifically, using a high-throughput screening platform with proprietary intellectual property rights, the inventors have identified a set of genes (termed "drug sensitivity genes") that, when mutated (e.g., inactivated) in colorectal cancer cells , sensitizes colorectal cancer cells (compared to colorectal cancer cells without such mutations) to treatment with DNA damaging agents such as PARP inhibitors or ATRi. The inventors have also identified a set of genes (termed "resistance genes") that, when mutated (eg, inactivated) in colorectal cancer cells, render colorectal cancer cells (compared to colorectal cancer cells without such mutations) Cancer cells) are more resistant to treatment with DNA damaging agents such as PARP inhibitors or ATRi. Abnormalities (e.g., mutations, aberrant expression, aberrant activity, and/or aberrant modifications (e.g., post-translational modifications)) in these genes can be useful for treating (or not treating) patients with DNA damaging agents (e.g., PARP inhibitors or ATRi). Useful biomarkers for individuals with colorectal cancer. For example, patients who carry mutations (e.g., inactivation) and/or reduced or absent drug-sensitivity gene expression (e.g., mRNA or protein) in the drug sensitivity genes described herein, compared to healthy individuals, and/or are associated with healthy individuals In contrast, patients with reduced or absent activity of drug-sensitive genes (eg, RNA or protein activity, eg due to epigenetic or post-translational modifications) are particularly suitable for treatment with corresponding anticancer drugs.

因此，本發明在一些實施方案中提供了一種藉由DNA損傷劑(例如PARP抑制劑或ATRi)治療結直腸癌的方法，其中所述治療基於本文所述的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的存在或不存在。在其他態樣，本文提供了基於本文所述的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如抗藥性異常)的存在或不存在來為患有結直腸癌的個體鑒定一種或多種治療選擇的方法，其中治療選擇包括含有投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療。在其他態樣，本文提供了基於本文所述的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的存在或不存在為患有結直腸癌的個體選擇治療的方法。在其他態樣，本文提供了基於本文所述的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的存在或不存在，預測用DNA損傷劑(例如PARP抑制劑或ATRi)治療患有結直腸癌的個體的生存期的方法。在其他態樣，本文提供了基於本文所述的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的存在或不存在鑒定可獲益於包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療的患有結直腸癌的個體的方法。Accordingly, the present invention provides, in some embodiments, a method of treating colorectal cancer with a DNA damaging agent such as a PARP inhibitor or ATRi, wherein said treatment is based on one or more of the drug sensitivity abnormalities described herein (e.g. Drug susceptibility mutations) and/or the presence or absence of drug resistance abnormalities (eg, drug resistance mutations). In other aspects, provided herein is the diagnosis of colorectal cancer based on the presence or absence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) and/or drug resistance abnormalities (eg, drug resistance abnormalities) described herein. A method of identifying one or more treatment options in an individual of , wherein the treatment options include treatment comprising administration of a DNA damaging agent (eg, a PARP inhibitor or ATRi). In other aspects, provided herein are patients with colorectal cancer based on the presence or absence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) and/or drug resistance abnormalities (eg, drug resistance mutations) described herein. The individual chooses the method of treatment. In other aspects, provided herein are prognostic DNA damaging agents based on the presence or absence of one or more of the drug sensitivity abnormalities (e.g. drug sensitivity mutations) and/or drug resistance abnormalities (e.g. drug resistance mutations) described herein. (eg, PARP inhibitors or ATRi) to treat the survival of individuals with colorectal cancer. In other aspects, provided herein is an identification based on the presence or absence of one or more of the drug sensitivity abnormalities (e.g. drug sensitivity mutations) and/or drug resistance abnormalities (e.g. drug resistance mutations) described herein that would benefit from the inclusion A method of administering treatment of a DNA damaging agent such as a PARP inhibitor or ATRi to an individual with colorectal cancer.

在其他態樣，本文提供了包含一個或多個處理器的系統；以及一種非暫時性電腦可讀存儲介體，其包含一個或多個可由一個或多個處理器執行的、用於運行本文描述的任意一種方法的程式。In other aspects, this document provides a system comprising one or more processors; and a non-transitory computer-readable storage medium comprising one or more processors executable by the one or more processors for running program for any of the methods described.

定義definition

如在本說明書和所附權利要求中使用的，除非內容另有明確規定，單數形式“一”、“一種”和“所述”（a, an, or the）包括複數指示物。因此，例如，提及“一個分子”任選地包括兩種或更多種此類分子的組合等。As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to "a molecule" optionally includes combinations of two or more such molecules, and the like.

除非上下文另有明確說明，術語“或”在本文中用於表示術語“和/或”，並且可與術語“和/或”互換使用。Unless the context clearly dictates otherwise, the term "or" is used herein to mean the term "and/or" and may be used interchangeably with the term "and/or".

如本文所用，術語“約”或“大約”是指本技術領域的技術人員容易知道的相應值的通常誤差範疇，例如，在給定量測性質或精度的情況下，是量測量的可接受程度的誤差或偏差。本文提及“約”或“大約”一個值或參數包括(並描述)針對該值或參數本身的實施方案。As used herein, the term "about" or "approximately" refers to the usual range of error for the corresponding value readily known to those skilled in the art, e.g., an acceptable range for a quantitative measurement given the nature or precision of the measurement. degree of error or deviation. Reference herein to "about" or "approximately" a value or parameter includes (and describes) embodiments directed to that value or parameter per se.

如本文所用，術語“配置為雜交”表示核酸分子具有與靶核酸的核苷酸序列具有足夠長度和序列互補性的核苷酸序列以允許核酸分子與靶核酸雜交，例如，在1x SCC(150 mM氯化鈉和15 mM檸檬酸三鈉)和0.1% SDS的水溶液中，Tm為至少65°C時。當將核酸分子與靶核酸分子雜交時，可以使用其他雜交條件，例如在所述方法的上下文中使用的條件。As used herein, the term "configured to hybridize" means that the nucleic acid molecule has a nucleotide sequence of sufficient length and sequence complementarity to the nucleotide sequence of the target nucleic acid to allow the nucleic acid molecule to hybridize to the target nucleic acid, e.g., at 1x SCC (150 mM sodium chloride and 15 mM trisodium citrate) and 0.1% SDS in water with a Tm of at least 65°C. Other hybridization conditions may be used when hybridizing a nucleic acid molecule to a target nucleic acid molecule, such as those used in the context of the methods described.

關於參比多肽或多核苷酸序列的“百分比(%)序列同一性”定義為，在比對序列和引入缺口（如果需要）以獲得最大百分比的序列同一性後，且不考慮將任何保守替換作為序列同一性的一部分的情況下，序列中與參比多肽或多核苷酸序列中的胺基酸殘基或核苷酸相同的胺基酸殘基或核苷酸的百分比。"Percent (%) sequence identity" with respect to a reference polypeptide or polynucleotide sequence is defined as, after aligning the sequences and introducing gaps, if necessary, to obtain the maximum percent sequence identity, and without taking into account any conservative substitutions As part of sequence identity, the percentage of amino acid residues or nucleotides in a sequence that are identical to those in a reference polypeptide or polynucleotide sequence.

“個體”或“個體”是哺乳動物。哺乳動物包括但不限於馴養動物(例如牛、綿羊、貓、狗和馬)、靈長類動物(例如人類和非人類靈長類動物例如猴子)、兔子和齧齒動物(例如小鼠和大鼠)。在某些實施方案中，所述個體或個體是人。在一些實施方案中，所述個體是人類患者，例如患有本文所述癌症的人類患者。An "individual" or "individual" is a mammal. Mammals include, but are not limited to, domesticated animals (such as cattle, sheep, cats, dogs, and horses), primates (such as humans and non-human primates such as monkeys), rabbits, and rodents (such as mice and rats) ). In certain embodiments, the individual or individual is a human. In some embodiments, the individual is a human patient, eg, a human patient with a cancer described herein.

如本文所用，“治療”(“treatment”或“treating”)是用於獲得有益或期望結果(包括臨床結果)的方法。對於本發明的目的，有益或期望的臨床結果包括但不限於以下一種或多種：減輕由疾病引起的一種或多種症狀、減輕疾病的程度、穩定疾病(例如，預防或延遲疾病惡化)、預防或延遲疾病的擴散(例如，轉移)、預防或延遲疾病的復發、延遲或減緩疾病的進展、改善疾病狀態、緩解(部分或全部)疾病、減少治療疾病所需的一種或多種其他藥物的劑量、延緩疾病進展、提高生活品質、和/或延長生存期。“治療”還包括減少癌症的病理結果。本發明的方法考慮了這些治療態樣的任何一個或多個態樣。As used herein, "treatment" or "treating" is a method used to obtain beneficial or desired results, including clinical results. For the purposes of this invention, beneficial or desired clinical outcomes include, but are not limited to, one or more of the following: alleviation of one or more symptoms caused by the disease, reduction of the extent of the disease, stabilization of the disease (e.g., prevention or delay of disease progression), prevention or Delay the spread of the disease (e.g., metastasis), prevent or delay the recurrence of the disease, delay or slow the progression of the disease, improve the disease state, alleviate (part or all) the disease, reduce the dose of one or more other drugs needed to treat the disease, Delay disease progression, improve quality of life, and/or prolong survival. "Treatment" also includes reducing the pathological consequences of cancer. The methods of the invention contemplate any one or more of these treatment modalities.

如本文所用，“延遲”癌症的進展是指推遲、阻礙、減緩、延緩、穩定和/或推遲疾病的發展。這種延遲可能有不同的時間長度，這取決於疾病的歷史和/或正在接受治療的個體。正如熟習此項技術者顯而易見的，充分或顯著的延遲實際上可以包括預防，因為個體不會患上疾病。“延遲”癌症發展的方法是與不使用所述方法相比，在給定時間範疇內降低疾病發展概率和/或在給定時間範疇內降低疾病程度的方法。這種比較通常基於臨床研究，使用統計學上顯著數量的個體。可以使用準則方法偵測癌症的發展，包括但不限於電腦軸向斷層掃描 (CAT Scan)、磁共振成像(MRI)、腹部超聲、凝血測試、動脈造影或活檢。所述進展也可以指最初不可偵測到的腫瘤進展，包括發生、復發和發作的。As used herein, "delaying" the progression of cancer means postponing, arresting, slowing, delaying, stabilizing and/or delaying the progression of the disease. This delay may be of varying lengths, depending on the history of the disease and/or the individual being treated. As will be apparent to those skilled in the art, a substantial or significant delay may actually include prevention, since the individual does not develop the disease. A method of "delaying" the development of cancer is a method of reducing the probability of disease development within a given time frame and/or reducing the extent of the disease within a given time frame compared to not using the method. Such comparisons are usually based on clinical studies, using a statistically significant number of individuals. Cancer development can be detected using standard methods including, but not limited to, computerized axial tomography (CAT Scan), magnetic resonance imaging (MRI), abdominal ultrasound, coagulation tests, arteriography, or biopsy. Progression can also refer to initially undetectable tumor progression, including onset, recurrence and flare-ups.

如本文所用，術語“有效量”是指足以治療特定病症、病狀或疾病（例如改善、緩和、減輕和/或延遲其一種或多種症狀）的化合物或組合物的量。對於治療用途，有益或期望的結果包括，例如，減少由疾病引起的一種或多種症狀(生化、組織學和/或行為)、包括在疾病發展過程中出現的併發症和中間病理表型、對那些患有疾病的人來說提高生活品質、減少治療疾病所需的其他藥物的劑量、增強另一種藥物的效果、延緩疾病的進展、和/或延長患者的生存期。關於癌症，有效量包括足以引起腫瘤組織收縮和/或降低腫瘤組織生長速率或防止或延遲腫瘤中其他不希望的細胞增殖的量。在一些實施方案中，有效量是足以延遲癌症發展的量。在一些實施方案中，有效量是足以防止或延遲復發的量。有效量可以一次或多次投予。在癌症的情況下，有效量的藥物或組合物可以：(i) 減少腫瘤細胞的數量； (ii) 減小腫瘤大小； (iii)在一定程度上抑制、延緩、減緩和較佳阻止腫瘤細胞浸潤到周圍器官；(iv)抑制(即在一定程度上減緩並較佳停止)腫瘤轉移；(v)抑制腫瘤生長；(vi)預防或延緩腫瘤的發生和/或復發；和/或(vii)在一定程度上緩解與癌症相關的一種或多種症狀。As used herein, the term "effective amount" refers to an amount of a compound or composition sufficient to treat a particular disorder, condition or disease (eg, ameliorate, alleviate, alleviate and/or delay one or more symptoms thereof). For therapeutic use, beneficial or desired results include, for example, reduction of one or more symptoms (biochemical, histological, and/or behavioral) caused by the disease, including complications and intermediate pathological phenotypes that arise during disease development, effects on For those with a disease, improve the quality of life, reduce the dose of other drugs needed to treat the disease, enhance the effect of another drug, slow the progression of the disease, and/or prolong the patient's survival. With respect to cancer, an effective amount includes an amount sufficient to cause tumor tissue to shrink and/or reduce the rate of growth of tumor tissue or prevent or delay otherwise undesired cellular proliferation in the tumor. In some embodiments, the effective amount is an amount sufficient to delay the development of cancer. In some embodiments, an effective amount is an amount sufficient to prevent or delay relapse. An effective amount can be administered once or multiple times. In the case of cancer, an effective amount of a drug or composition that: (i) reduces the number of tumor cells; (ii) reduces tumor size; (iii) inhibits, delays, slows down and preferably stops tumor cells to some extent Invasion into surrounding organs; (iv) inhibit (i.e. slow and preferably stop to some extent) tumor metastasis; (v) inhibit tumor growth; (vi) prevent or delay tumor occurrence and/or recurrence; and/or (vii ) alleviates to some extent one or more symptoms associated with cancer.

如本文所用，“可能有應答”或“應答性”是指臨床或非臨床的任何類型的改善或正回應，選自但不限於腫瘤大小或疾病或疾病進展證據的可量測的減小、完全緩解、部分緩解、疾病穩定、無進展生存期增加或延長，或總生存期增加或延長。As used herein, "likely to respond" or "responsiveness" refers to any type of improvement or positive response, clinical or non-clinical, selected from, but not limited to, measurable reduction in tumor size or evidence of disease or disease progression, Complete response, partial response, stable disease, increased or prolonged progression-free survival, or increased or prolonged overall survival.

如本文所用，“可”或“增加的可能性”是指事件、專案、物件、事物或人將發生的增加的概率。因此，在一個實例中，相對於參比個體或個體組，可能對抗癌療法(例如本文提供的抗癌療法)單獨或組合的治療有應答的個體對單獨或組合抗癌療法的治療有應答的可能性增加。相對於參比個體或個體群體，“不可”是指事件、專案、物件、事物或人發生的概率降低。因此，相對於參比個體或個體群體，不可對用抗癌療法(例如本文提供的抗癌療法單獨或組合)的治療應答的個體對用抗癌療法(單獨或組合)的治療應答的可能性降低。As used herein, "may" or "increased likelihood" refers to an increased probability that an event, item, thing, thing, or person will occur. Thus, in one example, an individual who is likely to respond to treatment with an anticancer therapy, such as an anticancer therapy provided herein, alone or in combination, is responsive to treatment with an anticancer therapy alone or in combination relative to a reference individual or group of individuals possibility increases. "Impossible" means that the probability of occurrence of an event, project, object, thing or person is reduced relative to a reference individual or group of individuals. Thus, the likelihood that an individual who is not responsive to treatment with an anticancer therapy (eg, an anticancer therapy provided herein, alone or in combination) will respond to treatment with an anticancer therapy (alone or in combination) relative to a reference individual or population of individuals reduce.

本文中的“倍增時間”或“群體倍增時間”(PDT)是指用於細胞群體大小倍增的時間。細胞倍增時間 = ln(2)/(增長率)。增長率(gr)是指單位時間內倍增的量。

Figure 02_image001
，其中N(t)為在時間t時的細胞數，N(0)為在時間0時的細胞數，t為時間(通常以小時為單位)。當細胞群是指數增長的群體時，即每個細胞在每個細胞週期中倍增，生長速率僅取決於細胞週期的長度，
Figure 02_image004
。 "Doubling time" or "population doubling time" (PDT) herein refers to the time for a population of cells to double in size. Cell doubling time = ln(2)/(growth rate). Growth rate (gr) refers to the amount of doubling per unit time.
Figure 02_image001
, where N(t) is the number of cells at time t, N(0) is the number of cells at time 0, and t is time (usually in hours). When the cell population is an exponentially growing population, i.e. each cell doubles every cell cycle, the growth rate depends only on the length of the cell cycle,
Figure 02_image004
.

如本文所用，“樣本”是指如本文所述從目的來源獲得或衍生的生物樣本。As used herein, "sample" refers to a biological sample obtained or derived from a source of interest as described herein.

本申請公開的方法The method disclosed in this application

本申請在一些實施方案中提供了鑒定患有結直腸癌的個體的方法，所述個體可獲益於包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療，所述方法包含在來自所述個體的樣本中偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)，其中，在所述樣本中一種或多種藥物敏感性異常（例如藥物敏感性突變）的存在，表明所述個體是可從所述治療中獲益的個體。The present application provides, in some embodiments, methods of identifying individuals with colorectal cancer who would benefit from treatment comprising administration of a DNA damaging agent (eg, a PARP inhibitor or ATRi) comprising One or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes are detected in a sample from the individual, wherein one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) are detected in the sample. The presence of a susceptibility mutation) indicates that the individual is one who may benefit from the treatment.

在一些實施方案中，本文提供了一種鑒定患有結直腸癌的個體的方法，所述個體不可獲益於包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療，所述方法包含在來自所述個體的樣本中偵測一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在將所述個體鑒定為不可從治療中獲益的個體。In some embodiments, provided herein is a method of identifying an individual with colorectal cancer who would not benefit from treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or ATRi), the method comprising in One or more drug resistance abnormalities (eg, drug resistance mutations) in one or more drug resistance genes are detected in a sample from said individual, wherein the presence of one or more drug resistance abnormalities (eg, drug resistance mutations) in said sample Such individuals are identified as those who would not benefit from treatment.

在一些實施方案中，本文提供了一種鑒定患有結直腸癌的個體的方法，所述個體可獲益於包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療，所述方法包含在來自所述個體的樣本中偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分將所述個體鑒定為可以從治療中獲益的個體。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of identifying an individual with colorectal cancer who would benefit from treatment comprising administering a DNA damaging agent (eg, a PARP inhibitor or ATRi), the method comprising in One or more drug sensitivity aberrations in one or more drug sensitivity genes (e.g., drug sensitivity mutations) and one or more drug resistance aberrations in one or more drug resistance genes ( e.g. drug resistance mutations), wherein a combined score of drug sensitivity abnormalities (e.g. drug sensitivity mutations) and drug resistance abnormalities (e.g. drug resistance mutations) above a threshold level identifies the individual as one who may benefit from treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了為患有結直腸癌的個體選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)，其中所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在確定包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療是適合個體的治療。In some embodiments, provided herein are methods of selecting treatment for an individual with colorectal cancer, the methods comprising detecting one or more drug sensitive genes in one or more drug sensitive genes in a sample from the individual Sexual abnormalities (such as drug sensitivity mutations), wherein the presence of one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in the sample determines that treatment comprising administration of DNA damaging agents (such as PARP inhibitors or ATRi) is suitable individual treatment.

在一些實施方案中，本文提供了為患有結直腸癌的個體選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在確定包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療是不適合所述個體的治療。In some embodiments, provided herein are methods of selecting treatment for an individual with colorectal cancer, the methods comprising detecting one or more drug resistance aberrations in one or more drug resistance genes in a sample from the individual (e.g., drug resistance mutations), wherein the presence of one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample determines that a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or ATRi) is inappropriate for the individual .

在一些實施方案中，本文提供了為患有結直腸癌的個體選擇治療的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中超過閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分確定包含投予DNA損傷劑(例如PARP抑制劑或ATRi)是適合所述個體的治療方法。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of selecting treatment for an individual with colorectal cancer, the methods comprising detecting one or more drug sensitive genes in one or more drug sensitive genes in a sample from the individual Sexual abnormalities (such as drug sensitivity mutations) and one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes, wherein above threshold levels of drug sensitivity abnormalities (such as drug sensitivity mutations) and resistance A composite score for a drug abnormality (eg, a drug resistance mutation) determines that a treatment comprising administration of a DNA damaging agent (eg, a PARP inhibitor or ATRi) is appropriate for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體確定一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)；和(b)至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)的存在生成報告，其中所述報告包含針對所述個體確定的一個或多個治療選擇，其中所述一個或多個治療選擇包含含有投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療。In some embodiments, provided herein is a method of determining one or more treatment options for an individual with colorectal cancer, the method comprising: (a) detecting one or more drug sensitive one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in a sex gene; and (b) generating a report based at least in part on the presence of one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in the sample, wherein The report comprises one or more treatment options determined for the individual, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent such as a PARP inhibitor or ATRi.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體識別一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)；和(b)至少部分基於所述樣本中一種或多種耐藥異常(例如耐藥突變)的存在生成報告，其中所述報告包含針對個體確定的一個或多個治療選擇，其中一種或多種治療選擇不包含含有投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療。In some embodiments, provided herein is a method of identifying one or more treatment options for an individual with colorectal cancer, the method comprising: (a) detecting one or more drug resistance in a sample from the individual one or more drug resistance aberrations (eg, drug resistance mutations) in a gene; and (b) generating a report based at least in part on the presence of one or more drug resistance aberrations (eg, drug resistance mutations) in the sample, wherein the report includes a reference to One or more treatment options determined by the individual, wherein one or more treatment options do not comprise a treatment comprising administration of a DNA damaging agent (eg, a PARP inhibitor or ATRi).

在一些實施方案中，本文提供了一種為患有結直腸癌的個體識別一種或多種治療選擇的方法，所述方法包含：(a)在來自所述個體的樣本中偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)；和(b)在來自所述個體的樣本中偵測一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)；和(c)至少部分基於所述樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和一種或多種耐藥異常(例如耐藥突變)的存在生成報告，其中所述報告包含針對所述個體確定的一個或多個治療選擇，其中所述一個或多個治療選擇包含含有投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療。在一些實施方案中，所述方法進一步包含獲得所述個體樣本中的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法進一步包含將綜合評分與閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of identifying one or more treatment options for an individual with colorectal cancer, the method comprising: (a) detecting one or more drug-sensitive one or more drug susceptibility abnormalities in one or more drug resistance genes (e.g. drug sensitivity mutations); and (b) detecting one or more drug resistance abnormalities in one or more drug resistance genes (e.g. drug resistance mutations); and (c) generating a report based at least in part on the presence of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) and one or more drug resistance abnormalities (e.g., drug resistance mutations) in the sample, wherein the The report comprises one or more treatment options determined for the individual, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (eg, a PARP inhibitor or ATRi). In some embodiments, the method further comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種為患有結直腸癌的個體選擇一種治療的方法，包含從來自個體的樣本中獲知一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)，其中回應所述獲知，(i)所述個體被歸類為接受包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療的候選人；和/或(ii)，所述個體被確定為對包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療做出反應。在一些實施方案中，本文提供了一種排除對患有結直腸癌的個體治療的方法，包括在來自個體的樣本中獲取一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的知識，其中響應所述獲知：(i)所述個體被歸類為不接受包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療的候選人；和/或(ii)所述個體被鑒定為對包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療不應答。在一些實施方案中，本文提供了一種為患有結直腸癌的個體選擇治療的方法，包含在來自個體的樣本中獲知一個或多個藥物敏感性基因的一種或多種藥物敏感性異常(例如藥物敏感性突變)和一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中回應所述獲知，(i)將所述個體歸類為接受包含投予DNA損傷劑(例如PARP抑制劑或ATRi)治療的候選人；和/或(ii)，所述個體被確定為對包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療應答。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法進一步包含將綜合評分與閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of selecting a treatment for an individual with colorectal cancer comprising learning from a sample from the individual one or more drug sensitivity aberrations in one or more drug sensitivity genes (e.g. drug sensitivity mutation), wherein in response to the learning, (i) the individual is classified as a candidate for treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or ATRi); and/or (ii), The individual is determined to respond to treatment comprising administration of a DNA damaging agent such as a PARP inhibitor or ATRi. In some embodiments, provided herein is a method of excluding treatment for an individual with colorectal cancer comprising obtaining one or more drug resistance aberrations in one or more drug resistance genes (e.g., drug resistance mutation), wherein in response to the knowledge: (i) the individual is classified as a candidate for treatment not to receive a treatment comprising administration of a DNA damaging agent (eg, a PARP inhibitor or ATRi); and/or (ii) the individual The individual is identified as non-responsive to treatment comprising administration of a DNA damaging agent such as a PARP inhibitor or ATRi. In some embodiments, provided herein is a method of selecting treatment for an individual with colorectal cancer comprising learning one or more drug sensitivity abnormalities in one or more drug sensitivity genes (e.g., drug sensitive mutation) and one or more resistance abnormalities (e.g., resistance mutations) in one or more resistance genes, wherein in response to said learning, (i) classifying said individual as receiving a DNA-damaging agent comprising administering ( Candidates for treatment such as a PARP inhibitor or ATRi); and/or (ii) the individual is determined to respond to a treatment comprising administration of a DNA damaging agent such as a PARP inhibitor or ATRi. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了預測患有結直腸癌、並經包含投予DNA損傷劑(例如PARP抑制劑或ATRi)治療的個體的生存期的方法，所述方法包含獲知來自所述個體的樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在使用DNA損傷劑(例如PARP抑制劑或ATRi)治療後具有更長的生存期。在一些實施方案中，本文提供了一種預測患有結直腸癌、並經包含投予DNA損傷劑(例如PARP抑制劑或ATRi)治療的個體的生存期的方法，所述方法包含獲知來自所述個體的樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中回應所述獲知，與在等效樣本中不具有所述一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體在用DNA損傷劑(例如PARP抑制劑或ATRi)治療後具有更長的生存期。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods of predicting survival in an individual with colorectal cancer treated comprising administering a DNA damaging agent (eg, a PARP inhibitor or ATRi), the method comprising knowing One or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes in a sample of which, in response to said learning, is the same as not having said one or more drug sensitivity in an equivalent sample Such individuals are predicted to have a longer survival after treatment with a DNA damaging agent such as a PARP inhibitor or ATRi compared to individuals with a sexual abnormality such as a drug sensitivity mutation. In some embodiments, provided herein is a method of predicting survival in an individual with colorectal cancer treated comprising administering a DNA damaging agent (e.g., a PARP inhibitor or ATRi), the method comprising knowing One or more drug sensitivity aberrations in one or more drug sensitivity genes (e.g., drug sensitivity mutations) and one or more drug resistance aberrations in one or more drug resistance genes (e.g., drug resistance mutations) in a sample from an individual ), wherein responsive to said learning, said individual is predicted to be active on DNA damaging agents (e.g., PARP inhibitory agent or ATRi) have a longer survival period. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體的方法，其包含：獲取識別個體中一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)的資訊，其中所述資訊將所述個體鑒定為適合於包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療。在一些實施方案中，本文提供了評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體的方法，其包含：獲取識別個體中一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊，其中所述資訊將所述個體鑒定為不適合於包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療。在一些實施方案中，本文提供了評估患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體的方法，其包含：獲取識別個體中一種或多種藥物敏感中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和個體中一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊，其中所述資訊(例如，高於閾值水準的藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分)將所述個體鑒定為適合於包含投予DNA損傷劑(例如PARP抑制劑或ATRi)的治療。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein are methods for evaluating an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility, colorectal cancer. A method comprising: obtaining information identifying one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes in an individual, wherein the information identifies the individual as suitable for comprising an administered Treatment with DNA damaging agents such as PARP inhibitors or ATRi. In some embodiments, provided herein are methods for evaluating an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility, colorectal cancer. A method comprising: obtaining information identifying one or more drug resistance abnormalities (eg, drug resistance mutations) in one or more drug resistance genes in an individual, wherein the information identifies the individual as unsuitable for comprising administering DNA damaging Treatment with agents such as PARP inhibitors or ATRi. In some embodiments, provided herein are methods for evaluating an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility, colorectal cancer. A method comprising: obtaining and identifying one or more drug sensitivity abnormalities in one or more drug sensitivity in an individual (eg, a drug sensitivity mutation) and one or more drug resistance abnormalities in one or more drug resistance genes in an individual (eg, drug resistance mutations), wherein the information (e.g., a composite score of drug sensitivity abnormalities (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) above a threshold level) identifies the individual as Treatments comprising administration of a DNA damaging agent such as a PARP inhibitor or ATRi are suitable. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了篩查患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體的方法，其包含獲知來自所述個體的樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常異常(例如藥物敏感性突變)，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體具有結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險降低。在一些實施方案中，本文提供了篩查患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體的方法，包含獲知來自個體的樣本中的一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中回應所述獲知，與不具有一種或多種耐藥異常(例如耐藥突變)的個體相比，預測所述個體具有結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或預後不良的風險增加。在一些實施方案中，本文提供了篩查患有結直腸癌、疑似患有結直腸癌、正在接受結直腸癌偵測、正在接受結直腸癌治療或正在接受結直腸癌易感性偵測的個體的方法，包含獲知來自所述個體樣本的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，其中回應所述獲知，與不具有一種或多種藥物敏感性異常(例如藥物敏感性突變)的個體相比，預測所述個體具有降低的結直腸癌復發、侵襲性結直腸癌、抗癌治療抗性或不良預後的風險。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述方法還包含將所述綜合評分與所述閾值水準進行比較。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is screening for an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to, colorectal cancer A method comprising learning of one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes in a sample from said individual, wherein in response to said learning, the same as not having a The individual is predicted to have a reduced risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis compared to individuals with abnormalities in one or more drug sensitivity (eg, drug sensitivity mutations). In some embodiments, provided herein is screening for an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to, colorectal cancer A method comprising learning one or more drug resistance aberrations (e.g., drug resistance mutations) in one or more drug resistance genes in a sample from an individual, wherein in response to said learning, one or more drug resistance aberrations (e.g., resistance mutations) are predicted to have an increased risk of colorectal cancer recurrence, invasive colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, provided herein is screening for an individual who has, is suspected of having, is being detected for, is being treated for, or is being detected for colorectal cancer susceptibility to, colorectal cancer A method comprising learning one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes and one or more drug resistance in one or more drug resistance genes from a sample of said individual Abnormalities (e.g., drug resistance mutations), wherein in response to the learning, the individual is predicted to have reduced colorectal cancer recurrence, aggressiveness, compared to individuals without one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) Risk of colorectal cancer, resistance to anticancer therapy, or poor prognosis. In some embodiments, the learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the sample from the individual. In some embodiments, the method further comprises comparing the composite score to the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，提供了一種治療個體結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑、ATRi)，其中，基於來自個體的樣本中的一個或多個藥物敏感性基因中具有一種或多種藥物敏感性異常(例如藥物敏感性突變)來選擇個體進行治療。在一些實施方案中，提供了一種治療個體結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑、ATRi)，其中基於所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準來選擇個體進行治療，其中所述藥物敏感性異常(例如藥物敏感性突變)是一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)並且其中耐藥異常(例如耐藥突變)是一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, there is provided a method of treating colorectal cancer in an individual comprising administering to the individual an effective amount of a DNA damaging agent (e.g., a PARP inhibitor, ATRi), wherein, based on a sample from the individual, one or Individuals are selected for treatment with one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in multiple drug sensitivity genes. In some embodiments, a method of treating colorectal cancer in an individual is provided, comprising administering to the individual an effective amount of a DNA damaging agent (e.g., a PARP inhibitor, ATRi), wherein an abnormality in drug sensitivity in a sample from the individual (e.g., drug sensitivity mutations) and drug resistance abnormalities (e.g., drug resistance mutations) are above a threshold level to select individuals for treatment, where the drug sensitivity abnormalities (e.g., drug sensitivity mutations) are one or more drug One or more drug sensitivity abnormalities (e.g. drug sensitivity mutations) in the sensitivity genes and wherein the drug resistance abnormalities (e.g. drug resistance mutations) are one or more drug resistance abnormalities (e.g. drug resistance mutations) in one or more drug resistance genes mutation). In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體結直腸癌的方法，包含獲知來自所述個體樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)，並且回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑或ATRi)。在一些實施方案中，本文提供了一種治療個體結直腸癌的方法，包括獲知來自所述個體樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，並回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual comprising learning of one or more drug sensitivity aberrations (e.g., drug sensitivity mutations) in one or more drug sensitivity genes in a sample from said individual ), and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (eg, a PARP inhibitor or ATRi). In some embodiments, provided herein is a method of treating colorectal cancer in an individual comprising learning of one or more drug sensitivity aberrations (e.g., drug sensitivity mutations) in one or more drug sensitivity genes in a sample from said individual ) and one or more resistance abnormalities (e.g., resistance mutations) in one or more resistance genes, and in response to said learning, administering to said individual an effective amount of a DNA damaging agent (e.g., a PARP inhibitor or ATRi) . In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，本文提供了一種治療個體的結直腸癌的方法，包含獲知個體樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)，並且回應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑或ATRi)。在一些實施方案中，本文提供了一種治療個體結直腸癌的方法，包含獲知個體樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，並且相應所述獲知，向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑或ATRi)。在一些實施方案中，所述獲知包含獲得所述個體樣本中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分。在一些實施方案中，所述個體中藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual comprising learning one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes in a sample from the individual, And in response to said learning, an effective amount of a DNA damaging agent (eg, a PARP inhibitor or ATRi) is administered to said individual. In some embodiments, provided herein is a method of treating colorectal cancer in an individual comprising knowing one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) in one or more drug sensitivity genes in a sample from the individual and a One or more drug resistance abnormalities (eg, drug resistance mutations) in one or more drug resistance genes, and in response to said knowledge, administering an effective amount of a DNA damaging agent (eg, PARP inhibitor or ATRi) to said individual. In some embodiments, said learning comprises obtaining a composite score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) in the individual sample. In some embodiments, the individual has a combined score of drug sensitivity abnormalities (eg, drug sensitivity mutations) and drug resistance abnormalities (eg, drug resistance mutations) above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在一些實施方案中，獲知個體樣本中一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，包含偵測樣本中一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)。In some embodiments, one or more drug sensitivity aberrations (e.g., drug sensitivity mutations) in one or more drug sensitivity genes and/or one or more resistance genes in one or more drug resistance genes are known in a sample from an individual. Drug sensitivity abnormalities (such as drug resistance mutations), including detection of one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in one or more drug sensitivity genes and/or detection of one or more drug sensitivity genes in a sample One or more resistance abnormalities (eg, resistance mutations).

在一些實施方案中，本文提供了一種治療個體結直腸癌的方法，In some embodiments, provided herein is a method of treating colorectal cancer in a subject,

包含偵測來自所述個體樣本中的一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，並向所述個體投予有效量的DNA損傷劑，例如PARP抑制劑或ATRi。comprising detecting one or more drug sensitivity aberrations (e.g., drug sensitivity mutations) in one or more drug sensitivity genes and/or one or more drug resistance genes in one or more drug resistance genes in a sample from said individual Drug abnormalities (eg, drug resistance mutations), and an effective amount of a DNA damaging agent, such as a PARP inhibitor or ATRi, is administered to the individual.

在一些實施方案中，本文提供了一種治療個體結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑或ATRi)，其中所述個體在一個或多個藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)。在一些實施方案中，本文提供了一種治療個體結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑(例如PARP抑制劑或ATRi)，其中所述個體在一個或多個藥物敏感性基因中包含一種或多種藥物敏感性異常(例如藥物敏感性突變)和在一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，並且其中所述藥物敏感性異常(例如藥物敏感性突變)和耐藥異常(例如耐藥突變)的綜合評分高於閾值水準。在一些實施方案中，所述綜合評分由公式I確定。在一些實施方案中，所述閾值水準為零。In some embodiments, provided herein is a method of treating colorectal cancer in an individual comprising administering to the individual an effective amount of a DNA damaging agent (e.g., a PARP inhibitor or ATRi), wherein the individual is on one or more agents One or more drug sensitivity abnormalities (eg, drug sensitivity mutations) are included in the susceptibility genes. In some embodiments, provided herein is a method of treating colorectal cancer in an individual comprising administering to the individual an effective amount of a DNA damaging agent (e.g., a PARP inhibitor or ATRi), wherein the individual is on one or more agents Contains one or more drug sensitivity abnormalities (such as drug sensitivity mutations) in the sensitivity gene and one or more drug resistance abnormalities (such as drug resistance mutations) in the one or more drug resistance genes, and wherein the drug sensitivity The combined score of abnormalities (such as drug sensitivity mutations) and drug resistance abnormalities (such as drug resistance mutations) is above the threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

在根據利用關於藥物敏感性基因的資訊的上述任何方法的一些實施方案中，一個或多個藥物敏感性基因選自表1中提供的藥物敏感性基因、或選自由表2提供的藥物敏感性基因組成的組。在一些實施方案中，所述一個或多個藥物敏感性基因包含表1或表2中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、150、200個基因或所有基因。In some embodiments according to any of the methods above using information about drug sensitivity genes, the one or more drug sensitivity genes are selected from the drug sensitivity genes provided in Table 1, or selected from the drug sensitivity genes provided in Table 2 group of genes. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200 genes or all genes.

表1. DNA損傷劑的藥物敏感性基因 基因功能 基因名稱 細胞蛋白修飾過程 ACTB、ALK、ANAPC7、ARNT、ARRB1、ASXL1、ATM、AXIN1、AXL、BAZ1A、BIRC6、BMP8B、BRCA1、BRCA2、CAB39、CBFB、CCNA2、CCND1、CDC25B、CDC42、CDK12、CDK2、CDKN1A、CHEK2、CKS1B、CKS2、CSF1、CSNK1E、CSNK1G1、CUL1、DBF4、DDIT4、DOT1L、DPM2、DSP、DTX1、DTX2、DTX4、DUSP4、DUSP5、ENC1、EP300、EPHA5、FANCM、FBXW11、FBXW7、FGF2、FGF23、FGFR4、FOXO1、GDF7、GSK3A、GSK3B、GUCY2D、HDAC2、HRAS、HSP90AA1、HSP90AB1、IL18、INS、KANSL1、KAT2A、KAT2B、KDM5C、KIDINS220、LAMB1、LATS2、LRP5、MAGI2、MAML1、MAPK12、MAPK14、MRGBP、NBN、NCK1、NF2、NFE2L1、NIPBL、NOG、PARP14、PARP2、PJA2、PLXNB2、PRKAA1、PRKDC、PTEN、PTP4A3、PTPN11、PTPRR、RNF213、RPS6KA2、RPS6KA5、SKP2、SMAD5、SMAD7、STAP1、STK11、TGFB1、TGFB2、TNF、TRAIP、TRIB3、TRIP12、TSC1、TSC2、UBE2T、UBR5、USP28、USP9X、WEE1、WNT7B、YWHAB、YWHAE 細胞分化 ACTA1、ACTB、ALK、ANK2、APCDD1、ARNT、ASXL1、ATM、AXL、BCL2L1、BMP8B、BRCA2、CBFB、CCND1、CDC25B、CDC42、CDK12、CDKN1A、CHD7、CR1、CSF1、CSNK1E、DDIT4、DICER1、DOK5、DROSHA、DSCAM、DSCAML1、DSP、DTX1、E2F1、ENC1、EP300、EPHA5、ETV4、FASLG、FBXW11、FBXW7、FGF2、FGF23、FOXO1、FOXO3、GDF7、GFRA1、GRB2、GSK3A、GSK3B、HDAC2、HLA-B、HOXB8、HPRT1、HSP90AA1、HSP90AB1、HSPG2、ID4、IL18、INS、KAT2A、KAT2B、KIAA1109、KIDINS220、LAMB1、LRP5、MAGI2、MAML1、MAPK12、MAPK14、NAV2、NCAM1、NCK1、NF2、NFATC4、NFE2L1、NIPBL、NOG、NUMB、PARP2、PLA2G2D、PLXNB2、PPARD、PRKDC、PTEN、PTPN11、RBM15、RBPJ、ROBO2、RPS6KA5、RUNX1、RUNX2、SAP30、SMAD5、SMAD7、STAP1、STK11、TCF7L2、TENM4、TGFB1、TGFB2、TGFBI、TNF、TRIB3、TSC1、USP9X、WEE1、WNT7B、YWHAE、ZEB1、ZFHX3 細胞增殖 ALK、ARID2、ARNT、ARRB1、ATM、BCL2L1、BIRC6、BRCA1、BRCA2、CCNA2、CCND1、CDC25B、CDC42、CDCA7、CDK2、CDKN1A、CKS1B、CKS2、CSF1、CUL1、DICER1、DLEC1、DOT1L、E2F1、FASLG、FBXW7、FGF2、FGF23、FGFR4、FOXO1、FOXO3、HDAC2、HPRT1、HRAS、ID4、IL18、INS、KAT2A、KAT2B、LAMB1、LRP5、MAGI2、MAPK14、NBN、NCK1、NF2、NOG、NRAS、NUMB、PBRM1、PHLDA2、PLA2G2D、PLXNB2、PPARD、PRKAA1、PRKDC、PTEN、RBM10、RBPJ、RPS6KA2、RUNX1、RUNX2、SKP2、SMAD7、STK11、TCF7L2、TENM4、TGFB1、TGFB2、TGFBI、TNF、TSC1、TSC2、USP28、WNT7B、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、ZEB1 免疫系統過程 ACTB、ARNT、ASXL1、ATM、AXL、BCL2L1、BRCA2、CAB39、CBFB、CD14、CDC42、CDKN1A、CHD7、CR1、CSF1、CUL1、DDIT4、DROSHA、DSP、DTX1、EP300、FASLG、FBXW11、FBXW7、FOXO3、GRB2、HLA-B、HOXB8、HPRT1、HRAS、HSP90AA1、HSP90AB1、IL18、INS、KAT2A、KAT2B、LRP5、MAPK14、NBN、NCAM1、NCK1、NFE2L1、NRAS、PARP14、PJA2、PLA2G2D、POLQ、PRKDC、PTPN11、RBM15、RBPJ、RPS6KA5、RUNX1、RUNX2、SKAP1、SKP2、SMAD5、SMAD7、STAP1、STK11、TGFB1、TGFB2、TNF、TP53BP1、TSC1、ZEB1 細胞死亡 AKAP12、ALK、ARRB1、ATM、AXIN1、AXL、BCL2L1、BIRC6、BRCA1、BRCA2、CD14、CDC42、CDCA7、CDKN1A、CHEK2、CSF1、CUL1、DDIT4、DICER1、DIDO1、DSP、E2F1、EP300、FASLG、FBXW7、FGF2、FOXO1、FOXO3、GSK3A、GSK3B、HDAC2、HRAS、HSP90AB1、INS、LATS2、LRP5、MAPK14、NBN、NCK1、NF2、NFATC4、NOG、PARP2、PEG3、PHLDA2、PPARD、PRKAA1、PRKDC、PTEN、RBM10、ROBO2、RPS6KA2、SKP2、STK11、TCF7L2、TGFB1、TGFB2、TNF、TRAIP、TRIB3、TSC1、TSC2、USP28、YWHAB、YWHAE 細胞週期 ACTB、ANAPC7、ATM、BCL2L1、BIRC6、BRCA1、BRCA2、CAB39、CCNA2、CCND1、CDC25B、CDC42、CDK12、CDK2、CDKN1A、CHEK2、CKS1B、CKS2、CSNK1E、CUL1、DBF4、DOT1L、E2F1、EP300、FANCM、FBXW11、FBXW7、HRAS、HSP90AA1、HSP90AB1、ID4、INS、KAT2A、KAT2B、KIF13A、LATS2、LRP5、MAGI2、MAPK12、MAPK14、NBN、NF2、NFE2L1、NIPBL、PBRM1、POLA1、PRKAA1、PRKDC、PTEN、PTPN11、RPS6KA2、SKP2、STK11、TCF7L2、TGFB1、TGFB2、TNF、TP53BP1、TSC1、TSC2、USP28、USP9X、WEE1、YWHAE、ZFHX3 Table 1. Drug susceptibility genes to DNA damaging agents gene function gene name Cellular Protein Modification Process ACTB, ALK, ANAPC7, ARNT, ARRB1, ASXL1, ATM, AXIN1, AXL, BAZ1A, BIRC6, BMP8B, BRCA1, BRCA2, CAB39, CBFB, CCNA2, CCND1, CDC25B, CDC42, CDK12, CDK2, CDKN1A, CHEK2, CKS1B, CKS2, CSF1, CSNK1E, CSNK1G1, CUL1, DBF4, DDIT4, DOT1L, DPM2, DSP, DTX1, DTX2, DTX4, DUSP4, DUSP5, ENC1, EP300, EPHA5, FANCM, FBXW11, FBXW7, FGF2, FGF23, FGFR4, FOXO1, GDF7, GSK3A, GSK3B, GUCY2D, HDAC2, HRAS, HSP90AA1, HSP90AB1, IL18, INS, KANSL1, KAT2A, KAT2B, KDM5C, KIDINS220, LAMB1, LATS2, LRP5, MAGI2, MAML1, MAPK12, MAPK14, MRGBP, NBN, NCK1, NF2, NFE2L1, NIPBL, NOG, PARP14, PARP2, PJA2, PLXNB2, PRKAA1, PRKDC, PTEN, PTP4A3, PTPN11, PTPRR, RNF213, RPS6KA2, RPS6KA5, SKP2, SMAD5, SMAD7, STAP1, STK11, TGFB1, TGFB2, TNF, TRAIP, TRIB3, TRIP12, TSC1, TSC2, UBE2T, UBR5, USP28, USP9X, WEE1, WNT7B, YWHAB, YWHAE Cell Differentiation ACTA1, ACTB, ALK, ANK2, APCDD1, ARNT, ASXL1, ATM, AXL, BCL2L1, BMP8B, BRCA2, CBFB, CCND1, CDC25B, CDC42, CDK12, CDKN1A, CHD7, CR1, CSF1, CSNK1E, DDIT4, DICER1, DOK5, DROSHA, DSCAM, DSCAML1, DSP, DTX1, E2F1, ENC1, EP300, EPHA5, ETV4, FASLG, FBXW11, FBXW7, FGF2, FGF23, FOXO1, FOXO3, GDF7, GFRA1, GRB2, GSK3A, GSK3B, HDAC2, HLA-B, Hoxb8, HPRT1, HSP90AA1, HSP90AB1, HSPG2, ID4, IL18, INS, KAT2A, KAT2B, Kiaa1109, Kidins220, LAMB1, LRP5, MAML1, MAPK12, MAPK14, NAV2,, Nav2, NCAM1, NCK1, NF2, NFATC4, NFE2L1, NIPBL, NOG, NUMB, PARP2, PLA2G2D, PLXNB2, PPARD, PRKDC, PTEN, PTPN11, RBM15, RBPJ, ROBO2, RPS6KA5, RUNX1, RUNX2, SAP30, SMAD5, SMAD7, STAP1, STK11, TCF7L2, TENM4, TGFB1, TGFB2, TGFBI, TNF, TRIB3, TSC1, USP9X, WEE1, WNT7B, YWHAE, ZEB1, ZFHX3 Cell Proliferation ALK, ARID2, ARNT, ARRB1, ATM, BCL2L1, BIRC6, BRCA1, BRCA2, CCNA2, CCND1, CDC25B, CDC42, CDCA7, CDK2, CDKN1A, CKS1B, CKS2, CSF1, CUL1, DICER1, DLEC1, DOT1L, E2F1, FASLG, FBXW7, FGF2, FGF23, FGFR4, FOXO1, FOXO3, HDAC2, HPRT1, HRAS, ID4, IL18, INS, KAT2A, KAT2B, LAMB1, LRP5, MAGI2, MAPK14, NBN, NCK1, NF2, NOG, NRAS, NUMB, PBRM1, PHLDA2, PLA2G2D, PLXNB2, PPARD, PRKAA1, PRKDC, PTEN, RBM10, RBPJ, RPS6KA2, RUNX1, RUNX2, SKP2, SMAD7, STK11, TCF7L2, TENM4, TGFB1, TGFB2, TGFBI, TNF, TSC1, TSC2, USP28, WNT7B, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, ZEB1 immune system process ACTB, ARNT, ASXL1, ATM, AXL, BCL2L1, BRCA2, CAB39, CBFB, CD14, CDC42, CDKN1A, CHD7, CR1, CSF1, CUL1, DDIT4, DROSHA, DSP, DTX1, EP300, FASLG, FBXW11, FBXW7, FOXO3, GRB2, HLA-B, HOXB8, HPRT1, HRAS, HSP90AA1, HSP90AB1, IL18, INS, KAT2A, KAT2B, LRP5, MAPK14, NBN, NCAM1, NCK1, NFE2L1, NRAS, PARP14, PJA2, PLA2G2D, POLQ, PRKDC, PTPN11, RBM15, RBPJ, RPS6KA5, RUNX1, RUNX2, SKAP1, SKP2, SMAD5, SMAD7, STAP1, STK11, TGFB1, TGFB2, TNF, TP53BP1, TSC1, ZEB1 cell death AKAP12, ALK, ARRB1, ATM, AXIN1, AXL, BCL2L1, BIRC6, BRCA1, BRCA2, CD14, CDC42, CDCA7, CDKN1A, CHEK2, CSF1, CUL1, DDIT4, DICER1, DIDO1, DSP, E2F1, EP300, FASLG, FBXW7, FGF2, FOXO1, FOXO3, GSK3A, GSK3B, HDAC2, HRAS, HSP90AB1, INS, LATS2, LRP5, MAPK14, NBN, NCK1, NF2, NFATC4, NOG, PARP2, PEG3, PHLDA2, PPARD, PRKAA1, PRKDC, PTEN, RBM10, ROBO2, RPS6KA2, SKP2, STK11, TCF7L2, TGFB1, TGFB2, TNF, TRAIP, TRIB3, TSC1, TSC2, USP28, YWHAB, YWHAE cell cycle ACTB, ANAPC7, ATM, BCL2L1, BIRC6, BRCA1, BRCA2, CAB39, CCNA2, CCND1, CDC25B, CDC42, CDK12, CDK2, CDKN1A, CHEK2, CKS1B, CKS2, CSNK1E, CUL1, DBF4, DOT1L, E2F1, EP300, FANCM, FBXW11, FBXW7, HRAS, HSP90AA1, HSP90AB1, ID4, INS, KAT2A, KAT2B, KIF13A, LATS2, LRP5, MAGI2, MAPK12, MAPK14, NBN, NF2, NFE2L1, NIPBL, PBRM1, POLA1, PRKAA1, PRKDC, PTEN, PTPN11, RPS6KA2, SKP2, STK11, TCF7L2, TGFB1, TGFB2, TNF, TP53BP1, TSC1, TSC2, USP28, USP9X, WEE1, YWHAE, ZFHX3

表2. DNA損傷劑的藥物敏感性基因 基因功能 基因名稱 細胞分化 ACTA1、ATM、CHD7、DSCAM、FBXW11、FBXW7、GFRA1、GSK3A、GSK3B、HDAC2、NFE2L1、PTEN、SMAD7、WEE1、YWHAE、ZFHX3 細胞週期 ATM、CDK2、FANCM、FBXW11、FBXW7、NBN、NFE2L1、PRKAA1、PTEN、WEE1、YWHAE、ZFHX3 細胞死亡 ATM、FBXW7、GSK3A、GSK3B、HDAC2、NBN、PRKAA1、PTEN、YWHAE 免疫系統過程 ATM、CHD7、FBXW11、FBXW7、NBN、NFE2L1、POLQ、SMAD7 細胞增殖 ATM、CDK2、FBXW7、HDAC2、NBN、PRKAA1、PTEN、SMAD7 細胞蛋白修飾過程 ATM、BAZ1A、CDK2、FANCM、FBXW11、FBXW7、GSK3A、GSK3B、HDAC2、KDM5C、NBN、NFE2L1、PRKAA1、PTEN、SMAD7、WEE1、YWHAE Table 2. Drug susceptibility genes to DNA damaging agents gene function gene name Cell Differentiation ACTA1, ATM, CHD7, DSCAM, FBXW11, FBXW7, GFRA1, GSK3A, GSK3B, HDAC2, NFE2L1, PTEN, SMAD7, WEE1, YWHAE, ZFHX3 cell cycle ATM, CDK2, FANCM, FBXW11, FBXW7, NBN, NFE2L1, PRKAA1, PTEN, WEE1, YWHAE, ZFHX3 cell death ATM, FBXW7, GSK3A, GSK3B, HDAC2, NBN, PRKAA1, PTEN, YWHAE immune system process ATM, CHD7, FBXW11, FBXW7, NBN, NFE2L1, POLQ, SMAD7 Cell Proliferation ATM, CDK2, FBXW7, HDAC2, NBN, PRKAA1, PTEN, SMAD7 Cellular Protein Modification Process ATM, BAZ1A, CDK2, FANCM, FBXW11, FBXW7, GSK3A, GSK3B, HDAC2, KDM5C, NBN, NFE2L1, PRKAA1, PTEN, SMAD7, WEE1, YWHAE

在根據利用關於藥物敏感性基因的資訊的上述任何方法的一些實施方案中，一個或多個藥物敏感性基因選自由表3提供的藥物敏感性基因組成的組。在一些實施方案中，所述一個或多個藥物敏感性基因包含表3中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90 、100、150、200個基因或所有基因。在根據利用關於藥物敏感性基因的資訊的上述任何方法的一些實施方案中，一個或多個藥物敏感性基因選自下組：ARID2、ARNT、ATM、BIRC6、BRCA1、BRCA2、CCNA2、CCND1、CDC25B、CDCA7、CDK2、CUL1、DICER1、DOT1L、E2F1、FBXW7、HDAC2、HRAS、KAT2B、NBN、NCK1、NF2、NRAS、PBRM1、PLXNB2、PPARD、PRKAA1、PTEN、RBM10、RBPJ、RUNX1、RUNX2、SKP2、SMAD7、TGFB2、TSC1、TSC2、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和ZEB1。在一些實施方案中，所述一個或多個藥物敏感性基因包含表3a)中提供的任意至少約1、2、5、10、15、20、25、30個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ATM、AXIN1、BIRC6、BRCA1、BRCA2、CD14、CDCA7、CUL1、DDIT4、DICER1、E2F1、FBXW7、GSK3A、GSK3B、HDAC2、HRAS、LATS2、NBN、NCK1、NF2、PPARD、PRKAA1、PTEN、RBM10、SKP2、TGFB2、TRAIP、TSC1、TSC2、和YWHAE。在一些實施方案中，所述一個或多個藥物敏感性基因包含表3b)中提供的任意至少約1、2、5、10、15、20個基因或所有基因中的任一種。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ATM、BIRC6、BRCA1、BRCA2、CAB39、CCNA2、CCND1、CDC25B、CDK2、CUL1、DBF4、DOT1L、E2F1、FANCM、FBXW11、FBXW7、HRAS、KAT2B、LATS2、NBN、NF2、NFE2L1、NIPBL、PBRM1、PRKAA1、PTEN、SKP2、TGFB2、TSC1、TSC2、USP9X、WEE1、YWHAE、和ZFHX3。在一些實施方案中，所述一個或多個藥物敏感性基因包含表3c)中提供的任意至少約1、2、5、10、15、20、25、30個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ARNT、ASXL1、ATM、BRCA2、CAB39、CBFB、CD14、CHD7、CUL1、DDIT4、DROSHA、FBXW11、FBXW7、HOXB8、HRAS、KAT2B、NBN、NCK1、NFE2L1、NRAS、PJA2、POLQ、RBM15、RBPJ、RUNX1、RUNX2、SKP2、SMAD5、SMAD7、STAP1、TGFB2、TSC1、和ZEB1。在一些實施方案中，所述一個或多個藥物敏感性基因包含表3d)中提供的任意至少約1、2、5、10、15、20、25、30個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ARNT、ASXL1、ATM、AXIN1、BAZ1A、BIRC6、BRCA1、BRCA2、CAB39、CBFB、CCNA2、CCND1、CDC25B、CDK2、CUL1、DBF4、DDIT4、DOT1L、DTX2、DUSP4、DUSP5、FANCM、FBXW11、FBXW7、GSK3A、GSK3B、HDAC2、HRAS、KAT2B、KDM5C、KIDINS220、LATS2、NBN、NCK1、NF2、NFE2L1、NIPBL、PJA2、PLXNB2、PRKAA1、PTEN、SKP2、SMAD5、SMAD7、STAP1、TGFB2、TRAIP、TRIP12、TSC1、TSC2、UBE2T、UBR5、USP9X、WEE1、YWHAE，ACTA1、ARNT、ASXL1、ATM、BRCA2、CBFB、CCND1、CDC25B、CHD7、DDIT4、DICER1、DROSHA、DSCAM、E2F1、ETV4、FBXW11、FBXW7、GFRA1、GSK3A、GSK3B、HDAC2、HOXB8、KAT2B、KIDINS220、NCK1、NF2、NFE2L1、NIPBL、PLXNB2、PPARD、PTEN、RBM15、RBPJ、RUNX1、RUNX2、SMAD5、SMAD7、STAP1、TGFB2、TSC1、USP9X、WEE1、YWHAE、ZEB1、和ZFHX3。在一些實施方案中，所述一個或多個藥物敏感性基因包含表3e)中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85 、90個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因包含表A中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。In some embodiments according to any of the above methods using information about drug sensitivity genes, the one or more drug sensitivity genes are selected from the group consisting of the drug sensitivity genes provided in Table 3. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60 , 70, 80, 90, 100, 150, 200 genes or all genes. In some embodiments according to any of the above methods using information about drug sensitivity genes, the one or more drug sensitivity genes are selected from the group consisting of: ARID2, ARNT, ATM, BIRC6, BRCA1, BRCA2, CCNA2, CCND1, CDC25B , CDCA7, CDK2, CUL1, DICER1, DOT1L, E2F1, FBXW7, HDAC2, HRAS, KAT2B, NBN, NCK1, NF2, NRAS, PBRM1, PLXNB2, PPARD, PRKAA1, PTEN, RBM10, RBPJ, RUNX1, RUNX2, SKP2, SMAD7 , TGFB2, TSC1, TSC2, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and ZEB1. In some embodiments, the one or more drug sensitivity genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30 or all of the genes provided in Table 3a). In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ATM, AXIN1, BIRC6, BRCA1, BRCA2, CD14, CDCA7, CUL1, DDIT4, DICER1, E2F1, FBXW7, GSK3A, GSK3B, HDAC2 , HRAS, LATS2, NBN, NCK1, NF2, PPARD, PRKAA1, PTEN, RBM10, SKP2, TGFB2, TRAIP, TSC1, TSC2, and YWHAE. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, or all of the genes provided in Table 3b). In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ATM, BIRC6, BRCA1, BRCA2, CAB39, CCNA2, CCND1, CDC25B, CDK2, CUL1, DBF4, DOT1L, E2F1, FANCM, FBXW11 , FBXW7, HRAS, KAT2B, LATS2, NBN, NF2, NFE2L1, NIPBL, PBRM1, PRKAA1, PTEN, SKP2, TGFB2, TSC1, TSC2, USP9X, WEE1, YWHAE, and ZFHX3. In some embodiments, the one or more drug sensitivity genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30 or all of the genes provided in Table 3c). In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ARNT, ASXL1, ATM, BRCA2, CAB39, CBFB, CD14, CHD7, CUL1, DDIT4, DROSHA, FBXW11, FBXW7, HOXB8, HRAS , KAT2B, NBN, NCK1, NFE2L1, NRAS, PJA2, POLQ, RBM15, RBPJ, RUNX1, RUNX2, SKP2, SMAD5, SMAD7, STAP1, TGFB2, TSC1, and ZEB1. In some embodiments, the one or more drug sensitivity genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30 or all of the genes provided in Table 3d). In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ARNT, ASXL1, ATM, AXIN1, BAZ1A, BIRC6, BRCA1, BRCA2, CAB39, CBFB, CCNA2, CCND1, CDC25B, CDK2, CUL1 , DBF4, DDIT4, DOT1L, DTX2, DUSP4, DUSP5, FANCM, FBXW11, FBXW7, GSK3A, GSK3B, HDAC2, HRAS, KAT2B, KDM5C, KIDINS220, LATS2, NBN, NCK1, NF2, NFE2L1, NIPBL, PJA2, PLXNB2, PRKAA1 , PTEN, SKP2, SMAD5, SMAD7, STAP1, TGFB2, TRAIP, TRIP12, TSC1, TSC2, UBE2T, UBR5, USP9X, WEE1, YWHAE, ACTA1, ARNT, ASXL1, ATM, BRCA2, CBFB, CCND1, CDC25B, CHD7, DDIT4 、DICER1、DROSHA、DSCAM、E2F1、ETV4、FBXW11、FBXW7、GFRA1、GSK3A、GSK3B、HDAC2、HOXB8、KAT2B、KIDINS220、NCK1、NF2、NFE2L1、NIPBL、PLXNB2、PPARD、PTEN、RBM15、RBPJ、RUNX1、RUNX2 , SMAD5, SMAD7, STAP1, TGFB2, TSC1, USP9X, WEE1, YWHAE, ZEB1, and ZFHX3. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 genes or all genes. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table A.

表3. PARPi的藥物敏感性基因 種類 基因功能 基因名稱 a) 細胞增殖 ARID2、ARNT、ATM、BIRC6、BRCA1、BRCA2、CCNA2、CCND1、CDC25B、CDCA7、CDK2、CUL1、DICER1、DOT1L、E2F1、FBXW7、HDAC2、HRAS、KAT2B、NBN、NCK1、NF2、NRAS、PBRM1、PLXNB2、PPARD、PRKAA1、PTEN、RBM10、RBPJ、RUNX1、RUNX2、SKP2、SMAD7、TGFB2、TSC1、TSC2、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、ZEB1 b) 細胞死亡 ATM、AXIN1、BIRC6、BRCA1、BRCA2、CD14、CDCA7、CUL1、DDIT4、DICER1、E2F1、FBXW7、GSK3A、GSK3B、HDAC2、HRAS、LATS2、NBN、NCK1、NF2、PPARD、PRKAA1、PTEN、RBM10、SKP2、TGFB2、TRAIP、TSC1、TSC2、YWHAE c) 細胞週期 ATM、BIRC6、BRCA1、BRCA2、CAB39、CCNA2、CCND1、CDC25B、CDK2、CUL1、DBF4、DOT1L、E2F1、FANCM、FBXW11、FBXW7、HRAS、KAT2B、LATS2、NBN、NF2、NFE2L1、NIPBL、PBRM1、PRKAA1、PTEN、SKP2、TGFB2、TSC1、TSC2、USP9X、WEE1、YWHAE、ZFHX3 d) 免疫系統過程 ARNT、ASXL1、ATM、BRCA2、CAB39、CBFB、CD14、CHD7、CUL1、DDIT4、DROSHA、FBXW11、FBXW7、HOXB8、HRAS、KAT2B、NBN、NCK1、NFE2L1、NRAS、PJA2、POLQ、RBM15、RBPJ、RUNX1、RUNX2、SKP2、SMAD5、SMAD7、STAP1、TGFB2、TSC1、ZEB1 e) 其他 ARNT、ASXL1、ATM、AXIN1、BAZ1A、BIRC6、BRCA1、BRCA2、CAB39、CBFB、CCNA2、CCND1、CDC25B、CDK2、CUL1、DBF4、DDIT4、DOT1L、DTX2、DUSP4、DUSP5、FANCM、FBXW11、FBXW7、GSK3A、GSK3B、HDAC2、HRAS、KAT2B、KDM5C、KIDINS220、LATS2、NBN、NCK1、NF2、NFE2L1、NIPBL、PJA2、PLXNB2、PRKAA1、PTEN、SKP2、SMAD5、SMAD7、STAP1、TGFB2、TRAIP、TRIP12、TSC1、TSC2、UBE2T、UBR5、USP9X、WEE1、YWHAE，ACTA1、ARNT、ASXL1、ATM、BRCA2、CBFB、CCND1、CDC25B、CHD7、DDIT4、DICER1、DROSHA、DSCAM、E2F1、ETV4、FBXW11、FBXW7、GFRA1、GSK3A、GSK3B、HDAC2、HOXB8、KAT2B、KIDINS220、NCK1、NF2、NFE2L1、NIPBL、PLXNB2、PPARD、PTEN、RBM15、RBPJ、RUNX1、RUNX2、SMAD5、SMAD7、STAP1、TGFB2、TSC1、USP9X、WEE1、YWHAE、ZEB1、ZFHX3 Table 3. Drug susceptibility genes of PARPi type gene function gene name a) Cell Proliferation ARID2, ARNT, ATM, BIRC6, BRCA1, BRCA2, CCNA2, CCND1, CDC25B, CDCA7, CDK2, CUL1, DICER1, DOT1L, E2F1, FBXW7, HDAC2, HRAS, KAT2B, NBN, NCK1, NF2, NRAS, PBRM1, PLXNB2, PPARD, PRKAA1, PTEN, RBM10, RBPJ, RUNX1, RUNX2, SKP2, SMAD7, TGFB2, TSC1, TSC2, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, ZEB1 b) cell death ATM, AXIN1, BIRC6, BRCA1, BRCA2, CD14, CDCA7, CUL1, DDIT4, DICER1, E2F1, FBXW7, GSK3A, GSK3B, HDAC2, HRAS, LATS2, NBN, NCK1, NF2, PPARD, PRKAA1, PTEN, RBM10, SKP2, TGFB2, TRAIP, TSC1, TSC2, YWHAE c) cell cycle ATM, BIRC6, BRCA1, BRCA2, CAB39, CCNA2, CCND1, CDC25B, CDK2, CUL1, DBF4, DOT1L, E2F1, FANCM, FBXW11, FBXW7, HRAS, KAT2B, LATS2, NBN, NF2, NFE2L1, NIPBL, PBRM1, PRKAA1, PTEN, SKP2, TGFB2, TSC1, TSC2, USP9X, WEE1, YWHAE, ZFHX3 d) immune system process ARNT, ASXL1, ATM, BRCA2, CAB39, CBFB, CD14, CHD7, CUL1, DDIT4, DROSHA, FBXW11, FBXW7, HOXB8, HRAS, KAT2B, NBN, NCK1, NFE2L1, NRAS, PJA2, POLQ, RBM15, RBPJ, RUNX1, RUNX2, SKP2, SMAD5, SMAD7, STAP1, TGFB2, TSC1, ZEB1 e) other ARNT, ASXL1, ATM, AXIN1, BAZ1A, BIRC6, BRCA1, BRCA2, CAB39, CBFB, CCNA2, CCND1, CDC25B, CDK2, CUL1, DBF4, DDIT4, DOT1L, DTX2, DUSP4, DUSP5, FANCM, FBXW11, FBXW7, GSK3A, GSK3B, HDAC2, HRAS, KAT2B, KDM5C, KIDINS220, LATS2, NBN, NCK1, NF2, NFE2L1, NIPBL, PJA2, PLXNB2, PRKAA1, PTEN, SKP2, SMAD5, SMAD7, STAP1, TGFB2, TRAIP, TRIP12, TSC1, TSC2, UBE2T, UBR5, USP9X, WEE1, YWHAE, ACTA1, ARNT, ASXL1, ATM, BRCA2, CBFB, CCND1, CDC25B, CHD7, DDIT4, DICER1, DROSHA, DSCAM, E2F1, ETV4, FBXW11, FBXW7, GFRA1, GSK3A, GSK3B, HDAC2, HOXB8, KAT2B, KIDINS220, NCK1, NF2, NFE2L1, NIPBL, PLXNB2, PPARD, PTEN, RBM15, RBPJ, RUNX1, RUNX2, SMAD5, SMAD7, STAP1, TGFB2, TSC1, USP9X, WEE1, YWHAE, ZEB1, ZFHX3

表A. PARPi的藥物敏感性基因 ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、ATRX Table A. Drug susceptibility genes of PARPi ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, ATRX

在根據利用關於藥物敏感性基因的資訊的上述任一方法的一些實施方案中，一個或多個藥物敏感性基因選自表4中提供的藥物敏感性基因。在一些實施方案中，所述一個或多個藥物敏感性基因包含表4中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90 、100、150、200、250、300個基因或所有基因。在根據利用關於藥物敏感性基因的資訊的上述任意方法的一些實施方案中，一個或多個藥物敏感性基因選自下組：ALK、ARRB1、ATM、BCL2L1、CDC42、CDK2、CDKN1A、CKS1B、CKS2、CSF1、DLEC1、FASLG、FBXW7、FGF2、FGF23、FGFR4、FOXO1、FOXO3、HDAC2、HPRT1、ID4、IL18、INS、KAT2A、LAMB1、LRP5、MAGI2、MAPK14、NBN、NOG、NUMB、PHLDA2、PLA2G2D、PRKAA1、PRKDC、PTEN、RPS6KA2、SMAD7、STK11、TCF7L2、TENM4、TGFB1、TGFBI、TNF、USP28、和WNT7B。在一些實施方案中，所述一個或多個藥物敏感性基因包含表4a)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：AKAP12、ALK、ARRB1、ATM、AXL、BCL2L1、CDC42、CDKN1A、CHEK2、CSF1、DIDO1、DSP、EP300、FASLG、FBXW7、FGF2、FOXO1、FOXO3、GSK3A、GSK3B、HDAC2、HSP90AB1、INS、LRP5、MAPK14、NBN、NFATC4、NOG、PARP2、PEG3、PHLDA2、PRKAA1、PRKDC、PTEN、ROBO2、RPS6KA2、STK11、TCF7L2、TGFB1、TNF、TRIB3、USP28、YWHAB、和YWHAE。在一些實施方案中，所述一個或多個藥物敏感性基因包含表4b)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ACTB、ANAPC7、ATM、BCL2L1、CDC42、CDK12、CDK2、CDKN1A、CHEK2、CKS1B、CKS2、CSNK1E、EP300、FANCM、FBXW11、FBXW7、HSP90AA1、HSP90AB1、ID4、INS、KAT2A、KIF13A、LRP5、MAGI2、MAPK12、MAPK14、NBN、NFE2L1、POLA1、PRKAA1、PRKDC、PTEN、PTPN11、RPS6KA2、STK11、TCF7L2、TGFB1、TNF、TP53BP1、USP28、WEE1、YWHAE、和ZFHX3。在一些實施方案中，所述一個或多個藥物敏感性基因包含表4c)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ACTB、ATM、AXL、BCL2L1、CDC42、CDKN1A、CHD7、CR1、CSF1、DSP、DTX1、EP300、FASLG、FBXW11、FBXW7、FOXO3、GRB2、HLA-B、HPRT1、HSP90AA1、HSP90AB1、IL18、INS、KAT2A、LRP5、MAPK14、NBN、NCAM1、NFE2L1、PARP14、PLA2G2D、POLQ、PRKDC、PTPN11、RPS6KA5、SKAP1、SMAD7、STK11、TGFB1、TNF、和TP53BP1。在一些實施方案中，所述一個或多個藥物敏感性基因包含表4d)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ACTA1、ACTB、ALK、ANK2、APCDD1、ATM、AXL、BCL2L1、BMP8B、CDC42、CDK12、CDKN1A、CHD7、CR1、CSF1、CSNK1E、DOK5、DSCAM、DSCAML1、DSP、DTX1、ENC1、EP300、EPHA5、FASLG、FBXW11、FBXW7、FGF2、FGF23、FOXO1、FOXO3、GDF7、GFRA1、GRB2、GSK3A、GSK3B、HDAC2、HLA-B、HPRT1、HSP90AA1、HSP90AB1、HSPG2、ID4、IL18、INS、KAT2A、KIAA1109、LAMB1、LRP5、MAGI2、MAML1、MAPK12、MAPK14、NAV2、NCAM1、NFATC4、NFE2L1、NOG、NUMB、PARP2、PLA2G2D、PRKDC、PTEN、PTPN11、ROBO2、RPS6KA5、SAP30、SMAD7、STK11、TCF7L2、TENM4、TGFB1、TGFBI、TNF、TRIB3、WEE1、WNT7B、YWHAE、和ZFHX3。在一些實施方案中，所述一個或多個藥物敏感性基因包含表4e)中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、55、60、65、70個基因或所有基因。在一些實施方案中，所述一個或多個藥物敏感性基因選自下組：ACTB、ALK、ANAPC7、ARRB1、ATM、AXL、BAZ1A、BMP8B、CDC42、CDK12、CDK2、CDKN1A、CHEK2、CKS1B、CKS2、CSF1、CSNK1E、CSNK1G1、DPM2、DSP、DTX1、DTX4、ENC1、EP300、EPHA5、FANCM、FBXW11、FBXW7、FGF2、FGF23、FGFR4、FOXO1、GDF7、GSK3A、GSK3B、GUCY2D、HDAC2、HSP90AA1、HSP90AB1、IL18、INS、KANSL1、KAT2A、KDM5C、LAMB1、LRP5、MAGI2、MAML1、MAPK12、MAPK14、MRGBP、NBN、NFE2L1、NOG、PARP14、PARP2、PRKAA1、PRKDC、PTEN、PTP4A3、PTPN11、PTPRR、RNF213、RPS6KA2、RPS6KA5、SMAD7、STK11、TGFB1、TNF、TRIB3、USP28、WEE1、WNT7B、YWHAB、和YWHAE。在一些實施方案中，所述一個或多個藥物敏感性基因包含表4f)中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、55、60、65、70個基因或所有基因。In some embodiments according to any of the methods above using information about drug sensitivity genes, the one or more drug sensitivity genes are selected from the drug sensitivity genes provided in Table 4. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60 , 70, 80, 90, 100, 150, 200, 250, 300 genes or all genes. In some embodiments according to any of the methods above using information about drug sensitivity genes, the one or more drug sensitivity genes are selected from the group consisting of: ALK, ARRB1, ATM, BCL2L1, CDC42, CDK2, CDKN1A, CKS1B, CKS2 , CSF1, DLEC1, FASLG, FBXW7, FGF2, FGF23, FGFR4, FOXO1, FOXO3, HDAC2, HPRT1, ID4, IL18, INS, KAT2A, LAMB1, LRP5, MAGI2, MAPK14, NBN, NOG, NUMB, PHLDA2, PLA2G2D, PRKAA1 , PRKDC, PTEN, RPS6KA2, SMAD7, STK11, TCF7L2, TENM4, TGFB1, TGFBI, TNF, USP28, and WNT7B. In some embodiments, the one or more drug sensitivity genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 4a) . In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of AKAP12, ALK, ARRB1, ATM, AXL, BCL2L1, CDC42, CDKN1A, CHEK2, CSF1, DIDO1, DSP, EP300, FASLG, FBXW7 , FGF2, FOXO1, FOXO3, GSK3A, GSK3B, HDAC2, HSP90AB1, INS, LRP5, MAPK14, NBN, NFATC4, NOG, PARP2, PEG3, PHLDA2, PRKAA1, PRKDC, PTEN, ROBO2, RPS6KA2, STK11, TCF7L2, TGFB1, TNF , TRIB3, USP28, YWHAB, and YWHAE. In some embodiments, the one or more drug sensitivity genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 4b) . In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ACTB, ANAPC7, ATM, BCL2L1, CDC42, CDK12, CDK2, CDKN1A, CHEK2, CKS1B, CKS2, CSNK1E, EP300, FANCM, FBXW11 , FBXW7, HSP90AA1, HSP90AB1, ID4, INS, KAT2A, KIF13A, LRP5, MAGI2, MAPK12, MAPK14, NBN, NFE2L1, POLA1, PRKAA1, PRKDC, PTEN, PTPN11, RPS6KA2, STK11, TCF7L2, TGFB1, TNF, TP53BP1 、USP28 , WEE1, YWHAE, and ZFHX3. In some embodiments, the one or more drug sensitivity genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 4c) . In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ACTB, ATM, AXL, BCL2L1, CDC42, CDKN1A, CHD7, CR1, CSF1, DSP, DTX1, EP300, FASLG, FBXW11, FBXW7 , FOXO3, GRB2, HLA-B, HPRT1, HSP90AA1, HSP90AB1, IL18, INS, KAT2A, LRP5, MAPK14, NBN, NCAM1, NFE2L1, PARP14, PLA2G2D, POLQ, PRKDC, PTPN11, RPS6KA5, SKAP1, SMAD7, STK11, TGFB1 , TNF, and TP53BP1. In some embodiments, the one or more drug sensitivity genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 4d) . In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ACTA1, ACTB, ALK, ANK2, APCDD1, ATM, AXL, BCL2L1, BMP8B, CDC42, CDK12, CDKN1A, CHD7, CR1, CSF1 , CSNK1E, DOK5, DSCAM, DSCAML1, DSP, DTX1, ENC1, EP300, EPHA5, FASLG, FBXW11, FBXW7, FGF2, FGF23, FOXO1, FOXO3, GDF7, GFRA1, GRB2, GSK3A, GSK3B, HDAC2, HLA-B, HPRT1 , HSP90AA1, HSP90AB1, HSPG2, ID4, IL18, INS, KAT2A, KIAA1109, LAMB1, LRP5, MAGI2, MAML1, MAPK12, MAPK14, NAV2, NCAM1, NFATC4, NFE2L1, NOG, NUMB, PARP2, PLA2G2D, PRKDC, PTEN, PTPN11 , ROBO2, RPS6KA5, SAP30, SMAD7, STK11, TCF7L2, TENM4, TGFB1, TGFBI, TNF, TRIB3, WEE1, WNT7B, YWHAE, and ZFHX3. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 genes or all genes. In some embodiments, the one or more drug sensitivity genes are selected from the group consisting of ACTB, ALK, ANAPC7, ARRB1, ATM, AXL, BAZ1A, BMP8B, CDC42, CDK12, CDK2, CDKN1A, CHEK2, CKS1B, CKS2 , CSF1, CSNK1E, CSNK1G1, DPM2, DSP, DTX1, DTX4, ENC1, EP300, EPHA5, FANCM, FBXW11, FBXW7, FGF2, FGF23, FGFR4, FOXO1, GDF7, GSK3A, GSK3B, GUCY2D, HDAC2, HSP90AA1, HSP90AB1, IL18 , INS, KANSL1, KAT2A, KDM5C, LAMB1, LRP5, MAGI2, MAML1, MAPK12, MAPK14, MRGBP, NBN, NFE2L1, NOG, PARP14, PARP2, PRKAA1, PRKDC, PTEN, PTP4A3, PTPN11, PTPRR, RNF213, RPS6KA2, RPS6KA5 , SMAD7, STK11, TGFB1, TNF, TRIB3, USP28, WEE1, WNT7B, YWHAB, and YWHAE. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 genes or all genes.

表4. ATRi藥物敏感性基因 種類 基因功能 基因名稱 a) 細胞增殖 ALK、ARRB1、ATM、BCL2L1、CDC42、CDK2、CDKN1A、CKS1B、CKS2、CSF1、DLEC1、FASLG、FBXW7、FGF2、FGF23、FGFR4、FOXO1、FOXO3、HDAC2、HPRT1、ID4、IL18、INS、KAT2A、LAMB1、LRP5、MAGI2、MAPK14、NBN、NOG、NUMB、PHLDA2、PLA2G2D、PRKAA1、PRKDC、PTEN、RPS6KA2、SMAD7、STK11、TCF7L2、TENM4、TGFB1、TGFBI、TNF、USP28、WNT7B b) 細胞死亡 AKAP12、ALK、ARRB1、ATM、AXL、BCL2L1、CDC42、CDKN1A、CHEK2、CSF1、DIDO1、DSP、EP300、FASLG、FBXW7、FGF2、FOXO1、FOXO3、GSK3A、GSK3B、HDAC2、HSP90AB1、INS、LRP5、MAPK14、NBN、NFATC4、NOG、PARP2、PEG3、PHLDA2、PRKAA1、PRKDC、PTEN、ROBO2、RPS6KA2、STK11、TCF7L2、TGFB1、TNF、TRIB3、USP28、YWHAB、YWHAE c) 細胞週期 ACTB、ANAPC7、ATM、BCL2L1、CDC42、CDK12、CDK2、CDKN1A、CHEK2、CKS1B、CKS2、CSNK1E、EP300、FANCM、FBXW11、FBXW7、HSP90AA1、HSP90AB1、ID4、INS、KAT2A、KIF13A、LRP5、MAGI2、MAPK12、MAPK14、NBN、NFE2L1、POLA1、PRKAA1、PRKDC、PTEN、PTPN11、RPS6KA2、STK11、TCF7L2、TGFB1、TNF、TP53BP1、USP28、WEE1、YWHAE、ZFHX3 d) 免疫系統過程 ACTB、ATM、AXL、BCL2L1、CDC42、CDKN1A、CHD7、CR1、CSF1、DSP、DTX1、EP300、FASLG、FBXW11、FBXW7、FOXO3、GRB2、HLA-B、HPRT1、HSP90AA1、HSP90AB1、IL18、INS、KAT2A、LRP5、MAPK14、NBN、NCAM1、NFE2L1、PARP14、PLA2G2D、POLQ、PRKDC、PTPN11、RPS6KA5、SKAP1、SMAD7、STK11、TGFB1、TNF、TP53BP1 e) 細胞分化 ACTA1、ACTB、ALK、ANK2、APCDD1、ATM、AXL、BCL2L1、BMP8B、CDC42、CDK12、CDKN1A、CHD7、CR1、CSF1、CSNK1E、DOK5、DSCAM、DSCAML1、DSP、DTX1、ENC1、EP300、EPHA5、FASLG、FBXW11、FBXW7、FGF2、FGF23、FOXO1、FOXO3、GDF7、GFRA1、GRB2、GSK3A、GSK3B、HDAC2、HLA-B、HPRT1、HSP90AA1、HSP90AB1、HSPG2、ID4、IL18、INS、KAT2A、KIAA1109、LAMB1、LRP5、MAGI2、MAML1、MAPK12、MAPK14、NAV2、NCAM1、NFATC4、NFE2L1、NOG、NUMB、PARP2、PLA2G2D、PRKDC、PTEN、PTPN11、ROBO2、RPS6KA5、SAP30、SMAD7、STK11、TCF7L2、TENM4、TGFB1、TGFBI、TNF、TRIB3、WEE1、WNT7B、YWHAE、ZFHX3 f) 細胞蛋白修飾過程 ACTB、ALK、ANAPC7、ARRB1、ATM、AXL、BAZ1A、BMP8B、CDC42、CDK12、CDK2、CDKN1A、CHEK2、CKS1B、CKS2、CSF1、CSNK1E、CSNK1G1、DPM2、DSP、DTX1、DTX4、ENC1、EP300、EPHA5、FANCM、FBXW11、FBXW7、FGF2、FGF23、FGFR4、FOXO1、GDF7、GSK3A、GSK3B、GUCY2D、HDAC2、HSP90AA1、HSP90AB1、IL18、INS、KANSL1、KAT2A、KDM5C、LAMB1、LRP5、MAGI2、MAML1、MAPK12、MAPK14、MRGBP、NBN、NFE2L1、NOG、PARP14、PARP2、PRKAA1、PRKDC、PTEN、PTP4A3、PTPN11、PTPRR、RNF213、RPS6KA2、RPS6KA5、SMAD7、STK11、TGFB1、TNF、TRIB3、USP28、WEE1、WNT7B、YWHAB、YWHAE Table 4. ATRi Drug Sensitivity Genes type gene function gene name a) Cell Proliferation ALK, ARRB1, ATM, BCL2L1, CDC42, CDK2, CDKN1A, CKS1B, CKS2, CSF1, DLEC1, FASLG, FBXW7, FGF2, FGF23, FGFR4, FOXO1, FOXO3, HDAC2, HPRT1, ID4, IL18, INS, KAT2A, LAMB1, LRP5, MAGI2, MAPK14, NBN, NOG, NUMB, PHLDA2, PLA2G2D, PRKAA1, PRKDC, PTEN, RPS6KA2, SMAD7, STK11, TCF7L2, TENM4, TGFB1, TGFBI, TNF, USP28, WNT7B b) cell death AKAP12, ALK, ARRB1, ATM, AXL, BCL2L1, CDC42, CDKN1A, CHEK2, CSF1, DIDO1, DSP, EP300, FASLG, FBXW7, FGF2, FOXO1, FOXO3, GSK3A, GSK3B, HDAC2, HSP90AB1, INS, LRP5, MAPK14, NBN, NFATC4, NOG, PARP2, PEG3, PHLDA2, PRKAA1, PRKDC, PTEN, ROBO2, RPS6KA2, STK11, TCF7L2, TGFB1, TNF, TRIB3, USP28, YWHAB, YWHAE c) cell cycle ACTB, ANAPC7, ATM, BCL2L1, CDC42, CDK12, CDK2, CDKN1A, CHEK2, CKS1B, CKS2, CSNK1E, EP300, FANCM, FBXW11, FBXW7, HSP90AA1, HSP90AB1, ID4, INS, KAT2A, KIF13A, LRP5, MAGI2, MAPK 12. MAPK14, NBN, NFE2L1, POLA1, PRKAA1, PRKDC, PTEN, PTPN11, RPS6KA2, STK11, TCF7L2, TGFB1, TNF, TP53BP1, USP28, WEE1, YWHAE, ZFHX3 d) immune system process ACTB, ATM, AXL, BCL2L1, CDC42, CDKN1A, CHD7, CR1, CSF1, DSP, DTX1, EP300, FASLG, FBXW11, FBXW7, FOXO3, GRB2, HLA-B, HPRT1, HSP90AA1, HSP90AB1, IL18, INS, KAT2A, LRP5, MAPK14, NBN, NCAM1, NFE2L1, PARP14, PLA2G2D, POLQ, PRKDC, PTPN11, RPS6KA5, SKAP1, SMAD7, STK11, TGFB1, TNF, TP53BP1 e) Cell Differentiation ACTA1, ACTB, ALK, ANK2, APCDD1, ATM, AXL, BCL2L1, BMP8B, CDC42, CDK12, CDKN1A, CHD7, CR1, CSF1, CSNK1E, DOK5, DSCAM, DSCAML1, DSP, DTX1, ENC1, EP300, EPHA5, FASLG, FBXW11, FBXW7, FGF2, FGF23, FOXO1, FOXO3, GDF7, GFRA1, GRB2, GSK3A, GSK3B, HDAC2, HLA-B, HPRT1, HSP90AA1, HSP90AB1, HSPG2, ID4, IL18, INS, KAT2A, KIAA1109, LAMB1, LRP5, MAGI2, MAML1, MAPK12, MAPK14, NAV2, NCAM1, NFATC4, NFE2L1, NOG, NUMB, PARP2, PLA2G2D, PRKDC, PTEN, PTPN11, ROBO2, RPS6KA5, SAP30, SMAD7, STK11, TCF7L2, TENM4, TGFB1, TGFBI, TNF, TRIB3, WEE1, WNT7B, YWHAE, ZFHX3 f) Cellular Protein Modification Process ACTB, ALK, ANAPC7, ARRB1, ATM, AXL, BAZ1A, BMP8B, CDC42, CDK12, CDK2, CDKN1A, CHEK2, CKS1B, CKS2, CSF1, CSNK1E, CSNK1G1, DPM2, DSP, DTX1, DTX4, ENC1, EP300, EPHA5, FANCM, FBXW11, FBXW7, FGF2, FGF23, FGFR4, FOXO1, GDF7, GSK3A, GSK3B, GUCY2D, HDAC2, HSP90AA1, HSP90AB1, IL18, INS, KANSL1, KAT2A, KDM5C, LAMB1, LRP5, MAGI2, MAML1, MAPK12, MAPK 14. MRGBP, NBN, NFE2L1, NOG, PARP14, PARP2, PRKAA1, PRKDC, PTEN, PTP4A3, PTPN11, PTPRR, RNF213, RPS6KA2, RPS6KA5, SMAD7, STK11, TGFB1, TNF, TRIB3, USP28, WEE1, WNT7B, YWHAB, YWHAE

在根據利用關於耐藥基因的資訊的上述任何方法的一些實施方案中，一個或多個耐藥基因選自表5中提供的耐藥基因，或選自由表6提供的耐藥基因組成的組。在一些實施方案中，所述一個或多個耐藥基因包含表5或表6中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90 、100、150、200個基因或所有基因。In some embodiments according to any of the above methods using information about drug resistance genes, the one or more drug resistance genes are selected from the drug resistance genes provided in Table 5, or selected from the group consisting of the drug resistance genes provided in Table 6 . In some embodiments, the one or more drug resistance genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 of the genes provided in Table 5 or Table 6. , 60, 70, 80, 90, 100, 150, 200 genes or all genes.

表5.DNA損傷劑的耐藥基因 基因功能 基因名稱 細胞蛋白修飾過程 ACVRL1、AKT1、ANAPC7、APC、BMP7、BMPR1A、BRAF、BRD4、BRPF3、BUB1、CBFB、CCNA1、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、CDKN1A、CHUK、CKS1B、CKS2、CREBBP、CRKL、CSNK1D、CSNK2A1、CTNNB1、CUL1、CUL9、DBF4、DDIT4、DNMT3B、DOT1L、DPM2、DUSP5、EGFR、EP300、EPHA5、EPHB4、FGF19、FGFR3、FRY、FZD1、GCN1L1、HDAC1、HIF1A、HSP90B1、IGF1R、IKBKG、ILK、INHA、JAK1、KMT2B、KMT2D、MAP3K4、MAPK1、MAPK14、MAPK3、MATK、MDM2、MED12、MLST8、MTOR、MUC17、MUC4、MUC5B、MYC、NCK1、NF2、NFKBIA、NPM1、NRG1、PARP1、PARP2、PDK2、PDPK1、PIK3CA、PLA2G6、PLCE1、PML、PPP2R1A、PPP2R1B、PRKAR1A、PTK2、PTPRH、RAC1、RAF1、RAPGEF1、RELA、RET、RHOA、RICTOR、ROCK2、RPS6KB1、RPS6KB2、RPTOR、SETD2、SKP2、SMAD2、SMAD4、SRC、STRADA、TIAM1、TP53、TSC1、USP28、USP9X、VHL、WWTR1、YES1 細胞分化 ACVRL1、AKAP6、AKT1、APC、ARID1A、BMP7、BMPR1A、CBFB、CCND1、CDC25B、CDH11、CDK1、CDKN1A、CHD2、CHUK、COMP、CR1、CREBBP、CRKL、CSNK1D、CTNNB1、CTNNBIP1、DDIT4、DLG5、DNMT3B、DOCK1、DOCK5、DOK4、E2F1、E2F4、EGFR、EIF2B2、EP300、EPHA5、EPHB4、FAM21C、FGF19、FGFR3、FMN2、FOXG1、FRY、FRYL、FZD1、GAB1、GNA11、HDAC1、HIF1A、ID1、ID2、ILK、INHA、KCNH1、KMT2B、KMT2D、LAMA5、MAP3K4、MAPK1、MAPK14、MAPK3、MDM2、MED12、MTOR、MYC、MYH9、MYO16、NCK1、NCSTN、NF2、NFKBIA、NRG1、PARP1、PARP2、PDPK1、PIK3CA、PLA2G3、PLCG1、PML、PPP2R1A、PRKAR1A、PTK2、PXN、RAC1、RAF1、RAPGEF1、RBL1、RELA、RET、RHEB、RHOA、ROCK2、SETD2、SMAD2、SMAD4、SMARCA2、SPTA1、SRC、TCF7L2、TENM3、TIAM1、TP53、TSC1、USP9X、VAV1、VHL、WWTR1、YAP1、YES1、ZMYND8 細胞增殖 ACVRL1、AKT1、APC、ARID2、BMP7、BMPR1A、BNIPL、BUB1、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、CDKN1A、CKS1B、CKS2、COMP、CRKL、CSNK2A1、CTNNB1、CTNNBIP1、CUL1、DLG5、DOT1L、E2F1、E2F3、E2F4、EGFR、FGF19、FGFR3、FOSL1、FOXG1、HDAC1、HIF1A、ID1、ID2、IGF1R、ILK、INHA、IRS1、KCNH1、KMT2D、LAMA5、MAPK1、MAPK14、MAPK3、MATK、MDM2、MTOR、MYC、MYO16、NCK1、NCSTN、NF2、NFKBIA、NPM1、NRG1、PBRM1、PDPK1、PLCG1、PML、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、RHOA、RICTOR、RPTOR、SKP2、SMAD2、SMAD4、SMARCA2、SPTA1、SRC、TCF7L2、TFDP1、TIAM1、TP53、TSC1、USP28、VHL、WWTR1、YAP1、Kras、YES1 細胞週期 AKT1、ANAPC7、APC、BMP7、BRD4、BUB1、CCNA1、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、CDKN1A、CKS1B、CKS2、CSNK1D、CSNK2A1、CTNNB1、CUL1、CUL9、DBF4、DOT1L、E2F1、E2F3、E2F4、EGFR、EIF4G2、EP300、FMN2、FOSL1、FOXG1、ID2、ILK、INHA、MAPK1、MAPK14、MAPK3、MDM2、MLST8、MTOR、MYC、MYH9、MYO16、NF2、NPM1、PBRM1、PML、PPP2R1A、PRKAR1A、RBL1、RHEB、RHOA、ROCK2、RPS6KB1、RPTOR、SETD2、SKP2、SRC、STRADA、TCF7L2、TFDP1、TP53、TP53BP1、TSC1、USP28、CDKN2A、CHEK1、SPTA1、PKMYT1、SIDT2、USP9X 免疫系統過程 AKT1、BCAR1、BMPR1A、CBFB、CDKN1A、CHD2、CHUK、CR1、CREBBP、CRKL、CTNNB1、CTNNBIP1、CUL1、DDIT4、DLG5、DOCK1、EIF2B2、EP300、HDAC1、HIF1A、ID2、IGF1R、IKBKG、INHA、JAK1、KMT2B、KMT2D、MAPK1、MAPK14、MAPK3、MT2A、MTOR、MUC17、MUC4、MUC5B、MYC、MYH2、MYH9、NCK1、NCSTN、NFKBIA、NLRC5、PARP1、PDPK1、PIK3CA、PIK3R2、PLA2G3、PLA2G6、PLCG1、PML、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、RET、RHOA、SETD2、SKP2、SPTA1、SRC、TNFRSF17、TP53、TP53BP1、TSC1、VAV1、YAP1、YES1 細胞死亡 AKT1、APC、BCAR1、BMP7、BNIPL、BRAF、BUB1、CCND2、CDK1、CDKN1A、COMP、CREBBP、CRKL、CSNK2A1、CTNNB1、CUL1、DDIT4、DLG5、DOCK1、E2F1、E2F3、EGFR、EIF4G2、EP300、FGFR3、FMN2、FOSL1、FZD1、HDAC1、HIF1A、HSP90B1、ID1、IGF1R、IKBKG、ILK、MAPK1、MAPK14、MAPK3、MDM2、MTOR、MYC、NCK1、NCSTN、NF2、NFKBIA、NPM1、PARP1、PARP2、PDK2、PDPK1、PIK3CA、PLA2G3、PLA2G6、PLCG1、PML、PPP2R1A、PPP2R1B、PSENEN、PTK2、PTPRH、RAF1、RELA、RET、RHOA、RPS6KB1、SKP2、SMAD4、SRC、TCF7L2、TFDP1、TIAM1、TP53、TSC1、USP28、VAV1、VHL、YAP1 Table 5. Resistance genes to DNA damaging agents gene function gene name Cellular Protein Modification Process ACVRL1, AKT1, ANAPC7, APC, BMP7, BMPR1A, BRAF, BRD4, BRPF3, BUB1, CBFB, CCNA1, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, CDKN1A, CHUK, CKS1B, CKS2, CREBBP, CRKL, CSNK1D, CSNK2A1, CTNNB1, CUL1, CUL9, DBF4, DDIT4, DNMT3B, DOT1L, DPM2, DUSP5, EGFR, EP300, EPHA5, EPHB4, FGF19, FGFR3, FRY, FZD1, GCN1L1, HDAC1, HIF1A, HSP90B1, IGF1R, IKBKG, ILK, INHA, JAK1, KMT2B, KMT2D, MAP3K4, MAPK1, MAPK14, MAPK3, MATK, MDM2, MED12, MLST8, MTOR, MUC17, MUC4, MUC5B, MYC, NCK1, NF2, NFKBIA, NPM1, NRG1, PARP1, PARP2, PDK2, PDPK1, PIK3CA, PLA2G6, PLCE1, PML, PPP2R1A, PPP2R1B, PRKAR1A, PTK2, PTPRH, RAC1, RAF1, RAPGEF1, RELA, RET, RHOA, RICTOR, ROCK2, RPS6KB1, RPS6KB2, RPTOR, SETD2, SKP2, SMAD2, SMAD4, SRC, STRADA, TIAM1, TP53, TSC1, USP28, USP9X, VHL, WWTR1, YES1 Cell Differentiation ACVRL1, AKAP6, AKT1, APC, ARID1A, BMP7, BMPR1A, CBFB, CCND1, CDC25B, CDH11, CDK1, CDKN1A, CHD2, CHUK, COMP, CR1, CREBBP, CRKL, CSNK1D, CTNNB1, CTNNBIP1, DDIT4, DLG5, DNMT3B, DOCK1, DOCK5, DOK4, E2F1, E2F4, EGFR, EIF2B2, EP300, EPHA5, EPHB4, FAM21C, FGF19, FGFR3, FMN2, FOXG1, FRY, FRYL, FZD1, GAB1, GNA11, HDAC1, HIF1A, ID1, ID2, ILK, INHA, KCNH1, KMT2B, KMT2D, LAMA5, MAP3K4, MAPK1, MAPK14, MAPK3, MDM2, MED12, MTOR, MYC, MYH9, MYO16, NCK1, NCSTN, NF2, NFKBIA, NRG1, PARP1, PARP2, PDPK1, PIK3CA, PLA2G3, PLCG1, PML, PPP2R1A, PRKAR1A, PTK2, PXN, RAC1, RAF1, RAPGEF1, RBL1, RELA, RET, RHEB, RHOA, ROCK2, SETD2, SMAD2, SMAD4, SMARCA2, SPTA1, SRC, TCF7L2, TENM3, TIAM1, TP53, TSC1, USP9X, VAV1, VHL, WWTR1, YAP1, YES1, ZMYND8 Cell Proliferation ACVRL1, AKT1, APC, ARID2, BMP7, BMPR1A, BNIPL, BUB1, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, CDKN1A, CKS1B, CKS2, COMP, CRKL, CSNK2A1, CTNNB1, CTNNBIP1, CUL1, DLG5, DOT1L, E2F1, E2F3, E2F4, EGFR, FGF19, FGFR3, FOSL1, FOXG1, HDAC1, HIF1A, ID1, ID2, IGF1R, ILK, INHA, IRS1, KCNH1, KMT2D, LAMA5, MAPK1, MAPK14, MAPK3, MATK, MDM2, MTOR, MYC, MYO16, NCK1, NCSTN, NF2, NFKBIA, NPM1, NRG1, PBRM1, PDPK1, PLCG1, PML, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1, RELA, RHOA, RICTOR, RPTOR, SKP2, SMAD2, SMAD4, SMARCA2, SPTA1, SRC, TCF7L2, TFDP1, TIAM1, TP53, TSC1, USP28, VHL, WWTR1, YAP1, Kras, YES1 cell cycle AKT1, ANAPC7, APC, BMP7, BRD4, BUB1, CCNA1, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, CDKN1A, CKS1B, CKS2, CSNK1D, CSNK2A1, CTNNB1, CUL1, CUL9, DBF4, DOT1L, E2F1, E2F3, E2F4, EGFR, EIF4G2, EP300, FMN2, FOSL1, FOXG1, ID2, ILK, INHA, MAPK1, MAPK14, MAPK3, MDM2, MLST8, MTOR, MYC, MYH9, MYO16, NF2, NPM1, PBRM1, PML, PPP2R1A, PRKAR1A, RBL1, RHEB, RHOA, ROCK2, RPS6KB1, RPTOR, SETD2, SKP2, SRC, STRADA, TCF7L2, TFDP1, TP53, TP53BP1, TSC1, USP28, CDKN2A, CHEK1, SPTA1, PKMYT1, SIDT2, USP9X immune system process AKT1, BCAR1, BMPR1A, CBFB, CDKN1A, CHD2, CHUK, CR1, CREBBP, CRKL, CTNNB1, CTNNBIP1, CUL1, DDIT4, DLG5, DOCK1, EIF2B2, EP300, HDAC1, HIF1A, ID2, IGF1R, IKBKG, INHA, JAK1, KMT2B, KMT2D, MAPK1, MAPK14, MAPK3, MT2A, MTOR, MUC17, MUC4, MUC5B, MYC, MYH2, MYH9, NCK1, NCSTN, NFKBIA, NLRC5, PARP1, PDPK1, PIK3CA, PIK3R2, PLA2G3, PLA2G6, PLCG1, PML, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1, RELA, RET, RHOA, SETD2, SKP2, SPTA1, SRC, TNFRSF17, TP53, TP53BP1, TSC1, VAV1, YAP1, YES1 cell death AKT1, APC, BCAR1, BMP7, BNIPL, BRAF, BUB1, CCND2, CDK1, CDKN1A, COMP, CREBBP, CRKL, CSNK2A1, CTNNB1, CUL1, DDIT4, DLG5, DOCK1, E2F1, E2F3, EGFR, EIF4G2, EP300, FGFR3, FMN2, FOSL1, FZD1, HDAC1, HIF1A, HSP90B1, ID1, IGF1R, IKBKG, ILK, MAPK1, MAPK14, MAPK3, MDM2, MTOR, MYC, NCK1, NCSTN, NF2, NFKBIA, NPM1, PARP1, PARP2, PDK2, PDPK1, PIK3CA, PLA2G3, PLA2G6, PLCG1, PML, PPP2R1A, PPP2R1B, PSENEN, PTK2, PTPRH, RAF1, RELA, RET, RHOA, RPS6KB1, SKP2, SMAD4, SRC, TCF7L2, TFDP1, TIAM1, TP53, TSC1, USP28, VAV1, VHL, YAP1

表6.DNA損傷劑的耐藥基因 基因功能 基因名稱 細胞分化 ACVRL1、AKT1、CHD2、CRKL、CTNNB1、GNA11、ID1、MAPK1、MED12、MYC、MYH9、PARP1、PIK3CA、PRKAR1A、RAF1、RAPGEF1、RHEB、SETD2、SMAD4、SRC、TP53、VAV1 細胞蛋白修飾過程 ACVRL1、AKT1、CRKL、CTNNB1、IGF1R、IKBKG、MAPK1、MED12、MLST8、MYC、PARP1、PIK3CA、PRKAR1A、RAF1、RAPGEF1、RICTOR、RPTOR、SETD2、SMAD4、SRC、TP53 免疫系統過程 AKT1、CHD2、CRKL、CTNNB1、IGF1R、IKBKG、MAPK1、MYC、MYH9、PARP1、PIK3CA、PIK3R2、PRKAR1A、RAF1、RAPGEF1、SETD2、SRC、TP53、VAV1 細胞增殖 ACVRL1、AKT1、CRKL、CTNNB1、E2F3、ID1、IGF1R、MAPK1、MYC、PRKAR1A、RAF1、RAPGEF1、RICTOR、RPTOR、SMAD4、SRC、TP53 細胞死亡 AKT1、CRKL、CTNNB1、E2F3、ID1、IGF1R、IKBKG、MAPK1、MYC、PARP1、PIK3CA、PSENEN、RAF1、SMAD4、SRC、TP53、VAV1 細胞週期 AKT1、CTNNB1、E2F3、MAPK1、MLST8、MYC、MYH9、PRKAR1A、RHEB、RPTOR、SETD2、SRC、TP53 Table 6. Resistance genes to DNA damaging agents gene function gene name Cell Differentiation ACVRL1, AKT1, CHD2, CRKL, CTNNB1, GNA11, ID1, MAPK1, MED12, MYC, MYH9, PARP1, PIK3CA, PRKAR1A, RAF1, RAPGEF1, RHEB, SETD2, SMAD4, SRC, TP53, VAV1 Cellular Protein Modification Process ACVRL1, AKT1, CRKL, CTNNB1, IGF1R, IKBKG, MAPK1, MED12, MLST8, MYC, PARP1, PIK3CA, PRKAR1A, RAF1, RAPGEF1, RICTOR, RPTOR, SETD2, SMAD4, SRC, TP53 immune system process AKT1, CHD2, CRKL, CTNNB1, IGF1R, IKBKG, MAPK1, MYC, MYH9, PARP1, PIK3CA, PIK3R2, PRKAR1A, RAF1, RAPGEF1, SETD2, SRC, TP53, VAV1 Cell Proliferation ACVRL1, AKT1, CRKL, CTNNB1, E2F3, ID1, IGF1R, MAPK1, MYC, PRKAR1A, RAF1, RAPGEF1, RICTOR, RPTOR, SMAD4, SRC, TP53 cell death AKT1, CRKL, CTNNB1, E2F3, ID1, IGF1R, IKBKG, MAPK1, MYC, PARP1, PIK3CA, PSENEN, RAF1, SMAD4, SRC, TP53, VAV1 cell cycle AKT1, CTNNB1, E2F3, MAPK1, MLST8, MYC, MYH9, PRKAR1A, RHEB, RPTOR, SETD2, SRC, TP53

在根據利用關於耐藥基因的資訊的上述任何方法的一些實施方案中，一個或多個耐藥基因選自由表7提供的耐藥基因組成的組。在一些實施方案中，所述一個或多個耐藥基因包含表7中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90 、100、150、200個基因或所有基因。在根據利用關於耐藥基因的資訊的上述任何方法的一些實施方案中，一個或多個耐藥基因選自下組：ACVRL1、AKT1、BMPR1A、BNIPL、BUB1、CDKN1A、CKS1B、CKS2、CRKL、CTNNB1、DLG5、E2F3、E2F4、FGF19、FOSL1、HDAC1、HIF1A、ID1、IGF1R、ILK、INHA、IRS1、KCNH1、MAPK1、MAPK14、MYC、MYO16、NCSTN、NFKBIA、NPM1、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、RICTOR、RPTOR、SMAD4、SMARCA2、SPTA1、SRC、TCF7L2、TP53、USP28、VHL、WWTR1、YAP1、Kras、和YES1。在一些實施方案中，所述一個或多個耐藥基因包含表7a)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：AKT1、BCAR1、BNIPL、BRAF、BUB1、CDKN1A、CREBBP、CRKL、CTNNB1、DLG5、E2F3、EP300、FOSL1、HDAC1、HIF1A、HSP90B1、ID1、IGF1R、IKBKG、ILK、MAPK1、MAPK14、MYC、NCSTN、NFKBIA、NPM1、PARP1、PARP2、PIK3CA、PPP2R1A、PSENEN、PTK2、RAF1、RELA、RPS6KB1、SMAD4、SRC、TCF7L2、TP53、USP28、VAV1、VHL、和YAP1。在一些實施方案中，所述一個或多個耐藥基因包含表7b)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：AKT1、ANAPC7、BUB1、CCNA1、CDKN1A、CKS1B、CKS2、CTNNB1、E2F3、E2F4、EP300、FOSL1、ILK、INHA、MAPK1、MAPK14、MLST8、MYC、MYH9、MYO16、NPM1、PPP2R1A、PRKAR1A、RBL1、RHEB、RPS6KB1、RPTOR、SETD2、SRC、TCF7L2、TP53、TP53BP1、CDKN2A、CHEK1、SPTA1、PKMYT1、SIDT2、和USP28。在一些實施方案中，所述一個或多個耐藥基因包含表7c)中提供的任意至少約1、2、5、10、15、20、25、30個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：AKT1、BCAR1、BMPR1A、CDKN1A、CHD2、CR1、CREBBP、CRKL、CTNNB1、DLG5、EIF2B2、EP300、HDAC1、HIF1A、IGF1R、IKBKG、INHA、KMT2B、MAPK1、MAPK14、MUC4、MYC、MYH9、NCSTN、NFKBIA、PARP1、PIK3CA、PIK3R2、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、SETD2、SPTA1、SRC、TP53、TP53BP1、VAV1、YAP1、和YES1。在一些實施方案中，所述一個或多個耐藥基因包含表7d)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：ACVRL1、AKAP6、AKT1、BMPR1A、CDH11、CDKN1A、CHD2、CR1、CREBBP、CRKL、CTNNB1、DLG5、DOCK5、E2F4、EIF2B2、EP300、EPHA5、FGF19、FRY、GNA11、HDAC1、HIF1A、ID1、ILK、INHA、KCNH1、KMT2B、MAP3K4、MAPK1、MAPK14、MED12、MYC、MYH9、MYO16、NCSTN、NFKBIA、PARP1、PARP2、PIK3CA、PPP2R1A、PRKAR1A、PTK2、PXN、RAC1、RAF1、RAPGEF1、RBL1、RELA、RHEB、SETD2、SMAD4、SMARCA2、SPTA1、SRC、TCF7L2、TP53、VAV1、VHL、WWTR1、YAP1、YES1、ZMYND8、ACVRL1、AKT1、ANAPC7、BMPR1A、BRAF、BRPF3、BUB1、CCNA1、CDKN1A、CKS1B、CKS2、CREBBP、CRKL、CTNNB1、DPM2、EP300、EPHA5、FGF19、FRY、GCN1L1、HDAC1、HIF1A、HSP90B1、IGF1R、IKBKG、ILK、INHA、KMT2B、MAP3K4、MAPK1、MAPK14、MED12、MLST8、MUC4、MYC、NFKBIA、NPM1、PARP1、PARP2、PIK3CA、PPP2R1A、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、RICTOR、RPS6KB1、RPS6KB2、RPTOR、SETD2、SMAD4、SRC、TP53、USP28、VHL、WWTR1、和YES1.在一些實施方案中，所述一個或多個耐藥基因包含表7e)中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95、100個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因包含表B中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45個基因或所有基因。In some embodiments according to any of the above methods using information about drug resistance genes, the one or more drug resistance genes are selected from the group consisting of the drug resistance genes provided in Table 7. In some embodiments, the one or more drug resistance genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200 genes or all genes. In some embodiments according to any of the above methods using information about drug resistance genes, the one or more drug resistance genes are selected from the group consisting of: ACVRL1, AKT1, BMPR1A, BNIPL, BUB1, CDKN1A, CKS1B, CKS2, CRKL, CTNNB1 , DLG5, E2F3, E2F4, FGF19, FOSL1, HDAC1, HIF1A, ID1, IGF1R, ILK, INHA, IRS1, KCNH1, MAPK1, MAPK14, MYC, MYO16, NCSTN, NFKBIA, NPM1, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1 , RELA, RICTOR, RPTOR, SMAD4, SMARCA2, SPTA1, SRC, TCF7L2, TP53, USP28, VHL, WWTR1, YAP1, Kras, and YES1. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 7a). In some embodiments, the one or more drug resistance genes are selected from the group consisting of AKT1, BCAR1, BNIPL, BRAF, BUB1, CDKN1A, CREBBP, CRKL, CTNNB1, DLG5, E2F3, EP300, FOSL1, HDAC1, HIF1A, HSP90B1, ID1, IGF1R, IKBKG, ILK, MAPK1, MAPK14, MYC, NCSTN, NFKBIA, NPM1, PARP1, PARP2, PIK3CA, PPP2R1A, PSENEN, PTK2, RAF1, RELA, RPS6KB1, SMAD4, SRC, TCF7L2, TP53, USP28, VAV1, VHL, and YAP1. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 7b). In some embodiments, the one or more drug resistance genes are selected from the group consisting of AKT1, ANAPC7, BUB1, CCNA1, CDKN1A, CKS1B, CKS2, CTNNB1, E2F3, E2F4, EP300, FOSL1, ILK, INHA, MAPK1, MAPK14, MLST8, MYC, MYH9, MYO16, NPM1, PPP2R1A, PRKAR1A, RBL1, RHEB, RPS6KB1, RPTOR, SETD2, SRC, TCF7L2, TP53, TP53BP1, CDKN2A, CHEK1, SPTA1, PKMYT1, SIDT2, and USP28. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30 or all of the genes provided in Table 7c). In some embodiments, the one or more drug resistance genes are selected from the group consisting of AKT1, BCAR1, BMPR1A, CDKN1A, CHD2, CR1, CREBBP, CRKL, CTNNB1, DLG5, EIF2B2, EP300, HDAC1, HIF1A, IGF1R, IKBKG, INHA, KMT2B, MAPK1, MAPK14, MUC4, MYC, MYH9, NCSTN, NFKBIA, PARP1, PIK3CA, PIK3R2, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1, RELA, SETD2, SPTA1, SRC, TP53, TP53BP1, VAV1, YAP1, and YES1. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 7d). In some embodiments, the one or more drug resistance genes are selected from the group consisting of ACVRL1, AKAP6, AKT1, BMPR1A, CDH11, CDKN1A, CHD2, CR1, CREBBP, CRKL, CTNNB1, DLG5, DOCK5, E2F4, EIF2B2, EP300, EPHA5, FGF19, FRY, GNA11, HDAC1, HIF1A, ID1, ILK, INHA, KCNH1, KMT2B, MAP3K4, MAPK1, MAPK14, MED12, MYC, MYH9, MYO16, NCSTN, NFKBIA, PARP1, PARP2, PIK3CA, PPP2R1A, PRKAR1A, PTK2, PXN, RAC1, RAF1, RAPGEF1, RBL1, RELA, RHEB, SETD2, SMAD4, SMARCA2, SPTA1, SRC, TCF7L2, TP53, VAV1, VHL, WWTR1, YAP1, YES1, ZMYND8, ACVRL1, AKT1, ANAPC7, BMPR1A, BRAF, BRPF3, BUB1, CCNA1, CDKN1A, CKS1B, CKS2, CREBBP, CRKL, CTNNB1, DPM2, EP300, EPHA5, FGF19, FRY, GCN1L1, HDAC1, HIF1A, HSP90B1, IGF1R, IKBKG, ILK, INHA, KMT2B, MAP3K4, MAPK1, MAPK14, MED12, MLST8, MUC4, MYC, NFKBIA, NPM1, PARP1, PARP2, PIK3CA, PPP2R1A, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1, RELA, RICTOR, RPS6KB1, RPS6KB2, RPTOR, SETD2, SMAD4, SRC, TP53, USP28, VHL, WWTR1, and YES1. In some embodiments, the one or more drug resistance genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 genes or all genes. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45 genes or all of the genes provided in Table B .

表7. PARPi耐藥基因 種類 基因功能 基因名稱 a) 細胞增殖 ACVRL1、AKT1、BMPR1A、BNIPL、BUB1、CDKN1A、CKS1B、CKS2、CRKL、CTNNB1、DLG5、E2F3、E2F4、FGF19、FOSL1、HDAC1、HIF1A、ID1、IGF1R、ILK、INHA、IRS1、KCNH1、MAPK1、MAPK14、MYC、MYO16、NCSTN、NFKBIA、NPM1、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、RICTOR、RPTOR、SMAD4、SMARCA2、SPTA1、SRC、TCF7L2、TP53、USP28、VHL、WWTR1、YAP1、Kras、YES1 b) 細胞死亡 AKT1、BCAR1、BNIPL、BRAF、BUB1、CDKN1A、CREBBP、CRKL、CTNNB1、DLG5、E2F3、EP300、FOSL1、HDAC1、HIF1A、HSP90B1、ID1、IGF1R、IKBKG、ILK、MAPK1、MAPK14、MYC、NCSTN、NFKBIA、NPM1、PARP1、PARP2、PIK3CA、PPP2R1A、PSENEN、PTK2、RAF1、RELA、RPS6KB1、SMAD4、SRC、TCF7L2、TP53、USP28、VAV1、VHL、YAP1 c) 細胞週期 AKT1、ANAPC7、BUB1、CCNA1、CDKN1A、CKS1B、CKS2、CTNNB1、E2F3、E2F4、EP300、FOSL1、ILK、INHA、MAPK1、MAPK14、MLST8、MYC、MYH9、MYO16、NPM1、PPP2R1A、PRKAR1A、RBL1、RHEB、RPS6KB1、RPTOR、SETD2、SRC、TCF7L2、TP53、TP53BP1、CDKN2A、CHEK1、SPTA1、PKMYT1、SIDT2、USP28 d) 免疫系統過程 AKT1、BCAR1、BMPR1A、CDKN1A、CHD2、CR1、CREBBP、CRKL、CTNNB1、DLG5、EIF2B2、EP300、HDAC1、HIF1A、IGF1R、IKBKG、INHA、KMT2B、MAPK1、MAPK14、MUC4、MYC、MYH9、NCSTN、NFKBIA、PARP1、PIK3CA、PIK3R2、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、SETD2、SPTA1、SRC、TP53、TP53BP1、VAV1、YAP1、YES1 e) 其他 ACVRL1、AKAP6、AKT1、BMPR1A、CDH11、CDKN1A、CHD2、CR1、CREBBP、CRKL、CTNNB1、DLG5、DOCK5、E2F4、EIF2B2、EP300、EPHA5、FGF19、FRY、GNA11、HDAC1、HIF1A、ID1、ILK、INHA、KCNH1、KMT2B、MAP3K4、MAPK1、MAPK14、MED12、MYC、MYH9、MYO16、NCSTN、NFKBIA、PARP1、PARP2、PIK3CA、PPP2R1A、PRKAR1A、PTK2、PXN、RAC1、RAF1、RAPGEF1、RBL1、RELA、RHEB、SETD2、SMAD4、SMARCA2、SPTA1、SRC、TCF7L2、TP53、VAV1、VHL、WWTR1、YAP1、YES1、ZMYND8、ACVRL1、AKT1、ANAPC7、BMPR1A、BRAF、BRPF3、BUB1、CCNA1、CDKN1A、CKS1B、CKS2、CREBBP、CRKL、CTNNB1、DPM2、EP300、EPHA5、FGF19、FRY、GCN1L1、HDAC1、HIF1A、HSP90B1、IGF1R、IKBKG、ILK、INHA、KMT2B、MAP3K4、MAPK1、MAPK14、MED12、MLST8、MUC4、MYC、NFKBIA、NPM1、PARP1、PARP2、PIK3CA、PPP2R1A、PRKAR1A、PTK2、RAC1、RAF1、RAPGEF1、RELA、RICTOR、RPS6KB1、RPS6KB2、RPTOR、SETD2、SMAD4、SRC、TP53、USP28、VHL、WWTR1、YES1 Table 7. PARPi resistance genes type gene function gene name a) Cell Proliferation ACVRL1, AKT1, BMPR1A, BNIPL, BUB1, CDKN1A, CKS1B, CKS2, CRKL, CTNNB1, DLG5, E2F3, E2F4, FGF19, FOSL1, HDAC1, HIF1A, ID1, IGF1R, ILK, INHA, IRS1, KCNH1, MAPK1, MAPK14, MYC, MYO16, NCSTN, NFKBIA, NPM1, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1, RELA, RICTOR, RPTOR, SMAD4, SMARCA2, SPTA1, SRC, TCF7L2, TP53, USP28, VHL, WWTR1, YAP1, Kras, YES1 b) cell death AKT1, BCAR1, BNIPL, BRAF, BUB1, CDKN1A, CREBBP, CRKL, CTNNB1, DLG5, E2F3, EP300, FOSL1, HDAC1, HIF1A, HSP90B1, ID1, IGF1R, IKBKG, ILK, MAPK1, MAPK14, MYC, NCSTN, NFKBIA, NPM1, PARP1, PARP2, PIK3CA, PPP2R1A, PSENEN, PTK2, RAF1, RELA, RPS6KB1, SMAD4, SRC, TCF7L2, TP53, USP28, VAV1, VHL, YAP1 c) cell cycle AKT1, ANAPC7, BUB1, CCNA1, CDKN1A, CKS1B, CKS2, CTNNB1, E2F3, E2F4, EP300, FOSL1, ILK, INHA, MAPK1, MAPK14, MLST8, MYC, MYH9, MYO16, NPM1, PPP2R1A, PRKAR1A, RBL1, RHEB, RPS6KB1, RPTOR, SETD2, SRC, TCF7L2, TP53, TP53BP1, CDKN2A, CHEK1, SPTA1, PKMYT1, SIDT2, USP28 d) immune system process AKT1, BCAR1, BMPR1A, CDKN1A, CHD2, CR1, CREBBP, CRKL, CTNNB1, DLG5, EIF2B2, EP300, HDAC1, HIF1A, IGF1R, IKBKG, INHA, KMT2B, MAPK1, MAPK14, MUC4, MYC, MYH9, NCSTN, NFKBIA, PARP1, PIK3CA, PIK3R2, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1, RELA, SETD2, SPTA1, SRC, TP53, TP53BP1, VAV1, YAP1, YES1 e) other ACVRL1, AKAP6, AKT1, BMPR1A, CDH11, CDKN1A, CHD2, CR1, CREBBP, CRKL, CTNNB1, DLG5, DOCK5, E2F4, EIF2B2, EP300, EPHA5, FGF19, FRY, GNA11, HDAC1, HIF1A, ID1, ILK, INHA, KCNH1, KMT2B, MAP3K4, MAPK1, MAPK14, MED12, MYC, MYH9, MYO16, NCSTN, NFKBIA, PARP1, PARP2, PIK3CA, PPP2R1A, PRKAR1A, PTK2, PXN, RAC1, RAF1, RAPGEF1, RBL1, RELA, RHEB, SETD2, SMAD4, SMARCA2, SPTA1, SRC, TCF7L2, TP53, VAV1, VHL, WWTR1, YAP1, YES1, ZMYND8, ACVRL1, AKT1, ANAPC7, BMPR1A, BRAF, BRPF3, BUB1, CCNA1, CDKN1A, CKS1B, CKS2, CREBBP, CRKL, CTNNB1, DPM2, EP300, EPHA5, FGF19, FRY, GCN1L1, HDAC1, HIF1A, HSP90B1, IGF1R, IKBKG, ILK, INHA, KMT2B, MAP3K4, MAPK1, MAPK14, MED12, MLST8, MUC4, MYC, NFKBIA, NPM1, PARP1, PARP2, PIK3CA, PPP2R1A, PRKAR1A, PTK2, RAC1, RAF1, RAPGEF1, RELA, RICTOR, RPS6KB1, RPS6KB2, RPTOR, SETD2, SMAD4, SRC, TP53, USP28, VHL, WWTR1, YES1

表B. PARPi的耐藥基因 PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、RBL1 Table B. Resistance genes of PARPi PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, RBL1

在根據利用關於耐藥基因的資訊的上述任何方法的一些實施方案中，一個或多個耐藥基因選自由表8提供的耐藥基因組成的組。在一些實施方案中，所述一個或多個耐藥基因包含表8中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、150、200、250、300個基因或所有基因。在根據利用關於耐藥基因的資訊的上述任何方法的一些實施方案中，一個或多個耐藥基因選自下組：ACVRL1、AKT1、APC、ARID2、BMP7、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、COMP、CRKL、CSNK2A1、CTNNB1、CTNNBIP1、CUL1、DOT1L、E2F1、E2F3、EGFR、FGFR3、FOXG1、ID1、ID2、IGF1R、KMT2D、LAMA5、MAPK1、MAPK3、MATK、MDM2、MTOR、MYC、NCK1、NF2、NRG1、PBRM1、PDPK1、PLCG1、PML、PRKAR1A、RAF1、RAPGEF1、RHOA、RICTOR、RPTOR、SKP2、SMAD2、SMAD4、SRC、TFDP1、TIAM1、TP53、和TSC1。在一些實施方案中，所述一個或多個耐藥基因包含表8a)中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：AKT1、APC、BMP7、CCND2、CDK1、COMP、CRKL、CSNK2A1、CTNNB1、CUL1、DDIT4、DOCK1、E2F1、E2F3、EGFR、EIF4G2、FGFR3、FMN2、FZD1、ID1、IGF1R、IKBKG、MAPK1、MAPK3、MDM2、MTOR、MYC、NCK1、NF2、PARP1、PDK2、PDPK1、PIK3CA、PLA2G3、PLA2G6、PLCG1、PML、PPP2R1B、PSENEN、PTPRH、RAF1、RET、RHOA、SKP2、SMAD4、SRC、TFDP1、TIAM1、TP53、TSC1、和VAV1。在一些實施方案中，所述一個或多個耐藥基因包含8b)中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：AKT1、APC、BMP7、BRD4、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、CSNK1D、CSNK2A1、CTNNB1、CUL1、CUL9、DBF4、DOT1L、E2F1、E2F3、EGFR、EIF4G2、FMN2、FOXG1、ID2、MAPK1、MAPK3、MDM2、MLST8、MTOR、MYC、MYH9、NF2、PBRM1、PML、PRKAR1A、RHEB、RHOA、ROCK2、RPTOR、SETD2、SKP2、SRC、STRADA、TFDP1、TP53、TSC1、和USP9X。在一些實施方案中，所述一個或多個耐藥基因包含表8c)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：AKT1、CBFB、CHD2、CHUK、CRKL、CTNNB1、CTNNBIP1、CUL1、DDIT4、DOCK1、ID2、IGF1R、IKBKG、JAK1、KMT2D、MAPK1、MAPK3、MT2A、MTOR、MUC17、MUC5B、MYC、MYH2、MYH9、NCK1、NLRC5、PARP1、PDPK1、PIK3CA、PIK3R2、PLA2G3、PLA2G6、PLCG1、PML、PRKAR1A、RAF1、RAPGEF1、RET、RHOA、SETD2、SKP2、SRC、TNFRSF17、TP53、TSC1、和VAV1。在一些實施方案中，所述一個或多個耐藥基因包含表8d)中提供的任意至少約1、2、5、10、15、20、25、30、35、40個基因或所有基因。在一些實施方案中，所述一個或多個耐藥基因選自下組：ACVRL1、AKT1、APC、BMP7、BRD4、CBFB、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、CHUK、CRKL、CSNK1D、CSNK2A1、CTNNB1、CUL1、CUL9、DBF4、DDIT4、DNMT3B、DOT1L、DUSP5、EGFR、EPHB4、FGFR3、FZD1、IGF1R、IKBKG、JAK1、KMT2D、MAPK1、MAPK3、MATK、MDM2、MED12、MLST8、MTOR、MUC17、MUC5B、MYC、NCK1、NF2、NRG1、PARP1、PDK2、PDPK1、PIK3CA、PLA2G6、PLCE1、PML、PPP2R1B、PRKAR1A、PTPRH、RAF1、RAPGEF1、RET、RHOA、RICTOR、ROCK2、RPTOR、SETD2、SKP2、SMAD2、SMAD4、SRC、STRADA、TIAM1、TP53、TSC1、USP9X、ACVRL1、AKT1、APC、ARID1A、BMP7、CBFB、CCND1、CDC25B、CDK1、CHD2、CHUK、COMP、CRKL、CSNK1D、CTNNB1、CTNNBIP1、DDIT4、DNMT3B、DOCK1、DOK4、E2F1、EGFR、EPHB4、FAM21C、FGFR3、FMN2、FOXG1、FRYL、FZD1、GAB1、GNA11、ID1、ID2、KMT2D、LAMA5、MAPK1、MAPK3、MDM2、MED12、MTOR、MYC、MYH9、NCK1、NF2、NRG1、PARP1、PDPK1、PIK3CA、PLA2G3、PLCG1、PML、PRKAR1A、RAF1、RAPGEF1、RET、RHEB、RHOA、ROCK2、SETD2、SMAD2、SMAD4、SRC、TENM3、TIAM1、TP53、TSC1、USP9X、和VAV1。在一些實施方案中，所述一個或多個耐藥基因包含表8e)中提供的任意至少約1、2、5、10、20、30、40、50、100個基因或所有基因。In some embodiments according to any of the above methods using information about drug resistance genes, the one or more drug resistance genes are selected from the group consisting of the drug resistance genes provided in Table 8. In some embodiments, the one or more drug resistance genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300 genes or all genes. In some embodiments of any of the above methods using information about drug resistance genes, the one or more drug resistance genes are selected from the group consisting of: ACVRL1, AKT1, APC, ARID2, BMP7, CCNA2, CCND1, CCND2, CCNE1, CDC25A , CDC25B, CDK1, COMP, CRKL, CSNK2A1, CTNNB1, CTNNBIP1, CUL1, DOT1L, E2F1, E2F3, EGFR, FGFR3, FOXG1, ID1, ID2, IGF1R, KMT2D, LAMA5, MAPK1, MAPK3, MATK, MDM2, MTOR, MYC , NCK1, NF2, NRG1, PBRM1, PDPK1, PLCG1, PML, PRKAR1A, RAF1, RAPGEF1, RHOA, RICTOR, RPTOR, SKP2, SMAD2, SMAD4, SRC, TFDP1, TIAM1, TP53, and TSC1. In some embodiments, the one or more drug resistance genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 genes provided in Table 8a) or all genes. In some embodiments, the one or more drug resistance genes are selected from the group consisting of AKT1, APC, BMP7, CCND2, CDK1, COMP, CRKL, CSNK2A1, CTNNB1, CUL1, DDIT4, DOCK1, E2F1, E2F3, EGFR, EIF4G2, FGFR3, FMN2, FZD1, ID1, IGF1R, IKBKG, MAPK1, MAPK3, MDM2, MTOR, MYC, NCK1, NF2, PARP1, PDK2, PDPK1, PIK3CA, PLA2G3, PLA2G6, PLCG1, PML, PPP2R1B, PSENEN, PTPRH, RAF1, RET, RHOA, SKP2, SMAD4, SRC, TFDP1, TIAM1, TP53, TSC1, and VAV1. In some embodiments, the one or more drug resistance genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 genes provided in 8b), or all genes. In some embodiments, the one or more drug resistance genes are selected from the group consisting of AKT1, APC, BMP7, BRD4, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, CSNK1D, CSNK2A1, CTNNB1, CUL1, CUL9, DBF4, DOT1L, E2F1, E2F3, EGFR, EIF4G2, FMN2, FOXG1, ID2, MAPK1, MAPK3, MDM2, MLST8, MTOR, MYC, MYH9, NF2, PBRM1, PML, PRKAR1A, RHEB, RHOA, ROCK2, RPTOR, SETD2, SKP2, SRC, STRADA, TFDP1, TP53, TSC1, and USP9X. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 8c). In some embodiments, the one or more drug resistance genes are selected from the group consisting of AKT1, CBFB, CHD2, CHUK, CRKL, CTNNB1, CTNNBIP1, CUL1, DDIT4, DOCK1, ID2, IGF1R, IKBKG, JAK1, KMT2D, MAPK1, MAPK3, MT2A, MTOR, MUC17, MUC5B, MYC, MYH2, MYH9, NCK1, NLRC5, PARP1, PDPK1, PIK3CA, PIK3R2, PLA2G3, PLA2G6, PLCG1, PML, PRKAR1A, RAF1, RAPGEF1, RET, RHOA, SETD2, SKP2, SRC, TNFRSF17, TP53, TSC1, and VAV1. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40 or all of the genes provided in Table 8d). In some embodiments, the one or more drug resistance genes are selected from the group consisting of ACVRL1, AKT1, APC, BMP7, BRD4, CBFB, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, CHUK, CRKL, CSNK1D, CSNK2A1, CTNNB1, CUL1, CUL9, DBF4, DDIT4, DNMT3B, DOT1L, DUSP5, EGFR, EPHB4, FGFR3, FZD1, IGF1R, IKBKG, JAK1, KMT2D, MAPK1, MAPK3, MATK, MDM2, MED12, MLST8, MTOR, MUC17, MUC5B, MYC, NCK1, NF2, NRG1, PARP1, PDK2, PDPK1, PIK3CA, PLA2G6, PLCE1, PML, PPP2R1B, PRKAR1A, PTPRH, RAF1, RAPGEF1, RET, RHOA, RICTOR, ROCK2, RPTOR, SETD2, SKP2, SMAD2, SMAD4, SRC, STRADA, TIAM1, TP53, TSC1, USP9X, ACVRL1, AKT1, APC, ARID1A, BMP7, CBFB, CCND1, CDC25B, CDK1, CHD2, CHUK, COMP, CRKL, CSNK1D, CTNNB1, CTNNBIP1, DDIT4, DNMT3B, DOCK1, DOK4, E2F1, EGFR, EPHB4, FAM21C, FGFR3, FMN2, FOXG1, FRYL, FZD1, GAB1, GNA11, ID1, ID2, KMT2D, LAMA5, MAPK1, MAPK3, MDM2, MED12, MTOR, MYC, MYH9, NCK1, NF2, NRG1, PARP1, PDPK1, PIK3CA, PLA2G3, PLCG1, PML, PRKAR1A, RAF1, RAPGEF1, RET, RHEB, RHOA, ROCK2, SETD2, SMAD2, SMAD4, SRC, TENM3, TIAM1, TP53, TSC1, USP9X, and VAV1. In some embodiments, the one or more drug resistance genes comprise any at least about 1, 2, 5, 10, 20, 30, 40, 50, 100 or all of the genes provided in Table 8e).

表8. ATRi耐藥基因 種類 基因功能 基因名稱 a) 細胞增殖 ACVRL1、AKT1、APC、ARID2、BMP7、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、COMP、CRKL、CSNK2A1、CTNNB1、CTNNBIP1、CUL1、DOT1L、E2F1、E2F3、EGFR、FGFR3、FOXG1、ID1、ID2、IGF1R、KMT2D、LAMA5、MAPK1、MAPK3、MATK、MDM2、MTOR、MYC、NCK1、NF2、NRG1、PBRM1、PDPK1、PLCG1、PML、PRKAR1A、RAF1、RAPGEF1、RHOA、RICTOR、RPTOR、SKP2、SMAD2、SMAD4、SRC、TFDP1、TIAM1、TP53、TSC1 b) 細胞死亡 AKT1、APC、BMP7、CCND2、CDK1、COMP、CRKL、CSNK2A1、CTNNB1、CUL1、DDIT4、DOCK1、E2F1、E2F3、EGFR、EIF4G2、FGFR3、FMN2、FZD1、ID1、IGF1R、IKBKG、MAPK1、MAPK3、MDM2、MTOR、MYC、NCK1、NF2、PARP1、PDK2、PDPK1、PIK3CA、PLA2G3、PLA2G6、PLCG1、PML、PPP2R1B、PSENEN、PTPRH、RAF1、RET、RHOA、SKP2、SMAD4、SRC、TFDP1、TIAM1、TP53、TSC1、VAV1 c) 細胞週期 AKT1、APC、BMP7、BRD4、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、CSNK1D、CSNK2A1、CTNNB1、CUL1、CUL9、DBF4、DOT1L、E2F1、E2F3、EGFR、EIF4G2、FMN2、FOXG1、ID2、MAPK1、MAPK3、MDM2、MLST8、MTOR、MYC、MYH9、NF2、PBRM1、PML、PRKAR1A、RHEB、RHOA、ROCK2、RPTOR、SETD2、SKP2、SRC、STRADA、TFDP1、TP53、TSC1、USP9X d) 免疫系統過程 AKT1、CBFB、CHD2、CHUK、CRKL、CTNNB1、CTNNBIP1、CUL1、DDIT4、DOCK1、ID2、IGF1R、IKBKG、JAK1、KMT2D、MAPK1、MAPK3、MT2A、MTOR、MUC17、MUC5B、MYC、MYH2、MYH9、NCK1、NLRC5、PARP1、PDPK1、PIK3CA、PIK3R2、PLA2G3、PLA2G6、PLCG1、PML、PRKAR1A、RAF1、RAPGEF1、RET、RHOA、SETD2、SKP2、SRC、TNFRSF17、TP53、TSC1、VAV1 e) 其他 ACVRL1、AKT1、APC、BMP7、BRD4、CBFB、CCNA2、CCND1、CCND2、CCNE1、CDC25A、CDC25B、CDK1、CHUK、CRKL、CSNK1D、CSNK2A1、CTNNB1、CUL1、CUL9、DBF4、DDIT4、DNMT3B、DOT1L、DUSP5、EGFR、EPHB4、FGFR3、FZD1、IGF1R、IKBKG、JAK1、KMT2D、MAPK1、MAPK3、MATK、MDM2、MED12、MLST8、MTOR、MUC17、MUC5B、MYC、NCK1、NF2、NRG1、PARP1、PDK2、PDPK1、PIK3CA、PLA2G6、PLCE1、PML、PPP2R1B、PRKAR1A、PTPRH、RAF1、RAPGEF1、RET、RHOA、RICTOR、ROCK2、RPTOR、SETD2、SKP2、SMAD2、SMAD4、SRC、STRADA、TIAM1、TP53、TSC1、USP9X、ACVRL1、AKT1、APC、ARID1A、BMP7、CBFB、CCND1、CDC25B、CDK1、CHD2、CHUK、COMP、CRKL、CSNK1D、CTNNB1、CTNNBIP1、DDIT4、DNMT3B、DOCK1、DOK4、E2F1、EGFR、EPHB4、FAM21C、FGFR3、FMN2、FOXG1、FRYL、FZD1、GAB1、GNA11、ID1、ID2、KMT2D、LAMA5、MAPK1、MAPK3、MDM2、MED12、MTOR、MYC、MYH9、NCK1、NF2、NRG1、PARP1、PDPK1、PIK3CA、PLA2G3、PLCG1、PML、PRKAR1A、RAF1、RAPGEF1、RET、RHEB、RHOA、ROCK2、SETD2、SMAD2、SMAD4、SRC、TENM3、TIAM1、TP53、TSC1、USP9X、VAV1 Table 8. ATRi resistance genes type gene function gene name a) Cell Proliferation ACVRL1, AKT1, APC, ARID2, BMP7, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, COMP, CRKL, CSNK2A1, CTNNB1, CTNNBIP1, CUL1, DOT1L, E2F1, E2F3, EGFR, FGFR3, FOXG1, ID1, ID2, IGF1R, KMT2D, LAMA5, MAPK1, MAPK3, MATK, MDM2, MTOR, MYC, NCK1, NF2, NRG1, PBRM1, PDPK1, PLCG1, PML, PRKAR1A, RAF1, RAPGEF1, RHOA, RICTOR, RPTOR, SKP2, SMAD2, SMAD4, SRC, TFDP1, TIAM1, TP53, TSC1 b) cell death AKT1, APC, BMP7, CCND2, CDK1, COMP, CRKL, CSNK2A1, CTNNB1, CUL1, DDIT4, DOCK1, E2F1, E2F3, EGFR, EIF4G2, FGFR3, FMN2, FZD1, ID1, IGF1R, IKBKG, MAPK1, MAPK3, MDM2, MTOR, MYC, NCK1, NF2, PARP1, PDK2, PDPK1, PIK3CA, PLA2G3, PLA2G6, PLCG1, PML, PPP2R1B, PSENEN, PTPRH, RAF1, RET, RHOA, SKP2, SMAD4, SRC, TFDP1, TIAM1, TP53, TSC1, VAV1 c) cell cycle AKT1, APC, BMP7, BRD4, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, CSNK1D, CSNK2A1, CTNNB1, CUL1, CUL9, DBF4, DOT1L, E2F1, E2F3, EGFR, EIF4G2, FMN2, FOXG1, ID2, MAPK1, MAPK3, MDM2, MLST8, MTOR, MYC, MYH9, NF2, PBRM1, PML, PRKAR1A, RHEB, RHOA, ROCK2, RPTOR, SETD2, SKP2, SRC, STRADA, TFDP1, TP53, TSC1, USP9X d) immune system process AKT1, CBFB, CHD2, CHUK, CRKL, CTNNB1, CTNNBIP1, CUL1, DDIT4, DOCK1, ID2, IGF1R, IKBKG, JAK1, KMT2D, MAPK1, MAPK3, MT2A, MTOR, MUC17, MUC5B, MYC, MYH2, MYH9, NCK1, NLRC5, PARP1, PDPK1, PIK3CA, PIK3R2, PLA2G3, PLA2G6, PLCG1, PML, PRKAR1A, RAF1, RAPGEF1, RET, RHOA, SETD2, SKP2, SRC, TNFRSF17, TP53, TSC1, VAV1 e) other ACVRL1, AKT1, APC, BMP7, BRD4, CBFB, CCNA2, CCND1, CCND2, CCNE1, CDC25A, CDC25B, CDK1, CHUK, CRKL, CSNK1D, CSNK2A1, CTNNB1, CUL1, CUL9, DBF4, DDIT4, DNMT3B, DOT1L, DUSP5, EGFR, EPHB4, FGFR3, FZD1, IGF1R, IKBKG, JAK1, KMT2D, MAPK1, MAPK3, MATK, MDM2, MED12, MLST8, MTOR, MUC17, MUC5B, MYC, NCK1, NF2, NRG1, PARP1, PDK2, PDPK1, PIK3CA, PLA2G6, PLCE1, PML, PPP2R1B, PRKAR1A, PTPRH, RAF1, RAPGEF1, RET, RHOA, RICTOR, ROCK2, RPTOR, SETD2, SKP2, SMAD2, SMAD4, SRC, STRADA, TIAM1, TP53, TSC1, USP9X, ACVRL1, AKT1, APC, ARID1A, BMP7, CBFB, CCND1, CDC25B, CDK1, CHD2, CHUK, COMP, CRKL, CSNK1D, CTNNB1, CTNNBIP1, DDIT4, DNMT3B, DOCK1, DOK4, E2F1, EGFR, EPHB4, FAM21C, FGFR3, FMN2, FOXG1, FRYL, FZD1, GAB1, GNA11, ID1, ID2, KMT2D, LAMA5, MAPK1, MAPK3, MDM2, MED12, MTOR, MYC, MYH9, NCK1, NF2, NRG1, PARP1, PDPK1, PIK3CA, PLA2G3, PLCG1, PML, PRKAR1A, RAF1, RAPGEF1, RET, RHEB, RHOA, ROCK2, SETD2, SMAD2, SMAD4, SRC, TENM3, TIAM1, TP53, TSC1, USP9X, VAV1

在根據本文描述的利用關於藥物敏感性基因和耐藥基因的資訊的任何方法的一些實施方案中，一個或多個藥物敏感性基因選自由表1提供的藥物敏感性基因組成的組，所述一個或多個耐藥基因選自由表5提供的耐藥基因組成的組。在一些實施方案中，所述一個或多個藥物敏感性基因包含表1提供的任意至少約1、2、5、10、15、20個基因或所有基因，和/或一個或多個耐藥基因包含表5提供的任意至少約1、2、5、10、15、20、25、30個基因或所有基因。在根據本文描述的利用關於藥物敏感性基因和耐藥基因的資訊的任意方法的一些實施方案中，所述一個或多個藥物敏感性基因選自表1提供的藥物敏感性基因，並且所述一個或多個耐藥基因選自表6提供的耐藥基因組成的組。在一些實施方案中，所述一個或多個藥物敏感性基因包含表1提供的任意至少約1、2、5、10、20個基因或所有基因，和/或一個或多個耐藥基因包含表6提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、150、200個基因或所有基因。在根據本文描述的利用關於藥物敏感性基因和耐藥基因的資訊的任何方法的一些實施方案中，一個或多個藥物敏感性基因選自表2提供的藥物敏感性基因組成的組，並且一個或多個耐藥基因選自表6提供的耐藥基因組成的組。在一些實施方案中，所述一個或多個藥物敏感性基因包含表2提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、150、200個基因或所有基因，和/或一個或多個耐藥基因包含表6中提供的任意至少約1、2、5、10、15、20、25、30、35、40、45、50、60、70、80、90、100、150、200個基因或所有基因。In some embodiments according to any of the methods described herein using information about drug sensitivity genes and drug resistance genes, the one or more drug sensitivity genes are selected from the group consisting of the drug sensitivity genes provided in Table 1, said The one or more drug resistance genes are selected from the group consisting of the drug resistance genes provided in Table 5. In some embodiments, the one or more drug susceptibility genes comprise any at least about 1, 2, 5, 10, 15, 20 genes or all genes provided in Table 1, and/or one or more drug resistance The genes comprise any at least about 1, 2, 5, 10, 15, 20, 25, 30 or all of the genes provided in Table 5. In some embodiments according to any of the methods described herein using information about drug sensitivity genes and drug resistance genes, said one or more drug sensitivity genes are selected from the drug sensitivity genes provided in Table 1, and said The one or more drug resistance genes are selected from the group consisting of drug resistance genes provided in Table 6. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 20 genes or all of the genes provided in Table 1, and/or the one or more drug resistance genes comprise Any at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200 or all of the genes provided in Table 6. In some embodiments according to any of the methods described herein using information about drug sensitivity genes and drug resistance genes, one or more drug sensitivity genes are selected from the group consisting of drug sensitivity genes provided in Table 2, and one or a plurality of drug resistance genes selected from the group consisting of the drug resistance genes provided in Table 6. In some embodiments, the one or more drug sensitivity genes comprise any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200 genes or all genes, and/or one or more drug resistance genes comprising any of at least about 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200 genes or all genes.

異常abnormal

基因(例如，靶基因、藥物敏感性基因、耐藥基因)的“異常”是指基因的遺傳和/或表觀遺傳異常、異常表達水準和/或異常活性水準，和/或基因(或基因產物，例如RNA或蛋白質)的異常修飾水準，其可能導致所述RNA和/或所述基因編碼的蛋白質功能異常喪失或功能降低和/或異常表達(例如，減少或缺失)。在一些實施方案中，遺傳異常包括核酸(例如DNA或RNA)或蛋白質序列(即突變)或與基因相關的異常表觀遺傳特徵的改變，包括但不限於編碼、非編碼、調節、強化子、沉默子、啟動子、內含子、外顯子和基因的非翻譯區。在一些實施方案中，基因的異常包括基因的突變，包括但不限於缺失、移碼、插入、插入缺失、錯義突變、無義突變、點突變、沉默突變、剪接位點突變、剪接變體、和易位。在一些實施方案中，所述突變可以是基因的丟失或缺失。在一些實施方案中，所述突變是有害突變。在一些實施方案中，與對照水準相比，基因的異常包括基因的異常(例如，減少或缺乏)表達(例如mRNA或蛋白質)。在一些實施方案中，與對照水準相比，基因的異常包括基因產物(例如，RNA或蛋白質)的異常活性(例如，降低或消失)，例如下游靶標的啟動或抑制。在一些實施方案中，與對照水準相比，基因的異常包括基因(例如，在DNA水準或組蛋白水準)或基因產物(例如，RNA或蛋白質)的異常修飾(例如，增加、減少或錯誤修飾)，例如翻譯後修飾(例如磷酸化、泛素化)。在一些實施方案中，基因的異常包括基因的拷貝數變化。在一些實施方案中，基因的拷貝數變化是由基因組的結構重排引起的，包括缺失、重複、倒置和易位。在一些實施方案中，基因的異常包括該基因的異常表觀遺傳特徵，包括但不限於DNA甲基化、羥甲基化、增加或減少的組蛋白結合、組蛋白甲基化、組蛋白乙醯化、染色質重塑等。在一些實施方案中，與對照或參照例如參照序列(例如核酸序列或蛋白質序列)、對照表達(例如RNA或蛋白質表達)水準、對照活性(例如下游標靶的啟動或抑制)水準、或對照修飾(例如，翻譯後修飾或表觀遺傳修飾)水準相比確定異常。在一些實施方案中，基因中的異常表達水準或異常活性水準可以低於對照水準(例如低於對照水準約10%、20%、30%、40%、60%、70%、80%、90 % 或更多)。在一些實施方案中，基因中的異常修飾水準(例如，DNA、核小體、RNA或蛋白質的修飾)可能低於對照水準(例如低於對照水準約10%、20%、30%、40%、60 %、70%、80%、90%或更多)、或高於對照水準(例如高於對照水準約 10%、20%、30%、40%、60%、70%、80%、90%或更多)。在一些實施方案中，基因中的異常修飾是錯誤修飾，例如泛素化而不是磷酸化。在一些實施方案中，對照水準(例如表達水準或活性水準或修飾水準)是對照群體的中值水準(例如表達水準或活性水準或修飾水準)。在一些實施方案中，對照群體是與正在/將被治療的個體具有相同癌症的群體。在一些實施方案中，對照群體是沒有癌症的健康群體，並且任選地具有與正在/將被治療的個體相當的人口統計學特徵(例如，性別、年齡、種族等)。在一些實施方案中，對照水準(例如表達水準或活性水準或修飾水準)是來自同一個體的健康組織的水準(例如表達水準或活性水準或修飾水準)。可以藉由與參比序列（包括對照樣本中參比序列的表觀遺傳模式）進行比較來確定基因的異常。在一些實施方案中，參比序列是對應於相應基因的全功能等位基因的序列(DNA、RNA或蛋白質序列)，例如存在於未患有癌症、但可以選擇性地具有與正在/將要治療的個體相似的人口統計學特徵(例如性別、年齡、種族等)的健康個體群體中的相應基因的等位基因(例如普遍等位基因)。An "abnormality" of a gene (e.g., a target gene, a drug sensitivity gene, a drug resistance gene) refers to a genetic and/or epigenetic abnormality, an abnormal expression level, and/or an abnormal activity level of a gene, and/or a gene (or gene product, such as RNA or protein), which may lead to abnormal loss of function or reduced function and/or abnormal expression (eg, reduction or deletion) of said RNA and/or protein encoded by said gene. In some embodiments, genetic abnormalities include alterations in nucleic acid (e.g., DNA or RNA) or protein sequences (i.e., mutations) or abnormal epigenetic features associated with genes, including but not limited to coding, noncoding, regulatory, enhancer, Silencers, promoters, introns, exons, and untranslated regions of genes. In some embodiments, abnormalities in genes include mutations in genes, including but not limited to deletions, frameshifts, insertions, indels, missense mutations, nonsense mutations, point mutations, silent mutations, splice site mutations, splice variants , and translocation. In some embodiments, the mutation may be a loss or deletion of a gene. In some embodiments, the mutation is a deleterious mutation. In some embodiments, an abnormality in a gene comprises abnormal (eg, reduced or absent) expression of a gene (eg, mRNA or protein) compared to a control level. In some embodiments, an abnormality in a gene comprises abnormal activity (eg, decreased or absent) of a gene product (eg, RNA or protein), such as activation or inhibition of a downstream target, compared to a control level. In some embodiments, abnormalities in genes include abnormal modifications (e.g., increases, decreases, or mismodifications) of genes (e.g., at the DNA level or histone levels) or gene products (e.g., RNA or proteins) compared to control levels. ), such as post-translational modifications (eg phosphorylation, ubiquitination). In some embodiments, the genetic abnormality comprises a copy number variation of the gene. In some embodiments, the copy number change of a gene results from a structural rearrangement of the genome, including deletions, duplications, inversions, and translocations. In some embodiments, abnormalities in a gene include abnormal epigenetic features of the gene, including but not limited to DNA methylation, hydroxymethylation, increased or decreased histone binding, histone methylation, histone B Acylation, chromatin remodeling, etc. In some embodiments, a control or reference such as a reference sequence (e.g., a nucleic acid sequence or protein sequence), a control expression (e.g., RNA or protein expression) level, a control activity (e.g., activation or inhibition of a downstream target) level, or a control modification (for example, post-translational modification or epigenetic modification) levels compared to determine abnormalities. In some embodiments, the level of aberrant expression or activity in a gene may be lower than a control level (e.g., about 10%, 20%, 30%, 40%, 60%, 70%, 80%, 90% lower than a control level). % Or more). In some embodiments, the level of abnormal modification (e.g., modification of DNA, nucleosomes, RNA, or protein) in the gene may be lower than the control level (e.g., about 10%, 20%, 30%, 40% lower than the control level , 60%, 70%, 80%, 90% or more), or above the control level (for example, about 10%, 20%, 30%, 40%, 60%, 70%, 80% above the control level, 90% or more). In some embodiments, the abnormal modification in the gene is a wrong modification, such as ubiquitination instead of phosphorylation. In some embodiments, the control level (eg, expression level or activity level or modification level) is the median level (eg, expression level or activity level or modification level) of a control population. In some embodiments, the control population is a population having the same cancer as the individual being/to be treated. In some embodiments, the control population is a healthy population without cancer, and optionally has comparable demographic characteristics (eg, gender, age, race, etc.) to the individual being/to be treated. In some embodiments, the control level (eg, expression level or activity level or modification level) is a level (eg, expression level or activity level or modification level) from healthy tissue of the same individual. Genetic abnormalities can be determined by comparison to a reference sequence, including the epigenetic pattern of the reference sequence in a control sample. In some embodiments, the reference sequence is a sequence (DNA, RNA or protein sequence) that corresponds to a fully functional allele of the corresponding gene, such as that present in a patient not suffering from cancer, but optionally having a relationship with being/to be treated Alleles (eg, prevalent alleles) of the corresponding gene in a population of healthy individuals whose individuals have similar demographic characteristics (eg, sex, age, race, etc.).

靶基因的異常在本文中也稱為“靶基因異常”，包括但不限於靶基因突變。藥物敏感性基因的異常在本文中也稱為“藥物敏感性異常”，包括但不限於藥物敏感性突變，其使癌細胞對抗癌藥物(例如DNA損傷劑如PARPi或ATRi)敏感。耐藥基因的異常在本文中也稱為“耐藥異常”，包括但不限於耐藥突變，其使癌細胞對抗癌藥物(例如，DNA損傷劑如PARPi或ATRi)耐藥。患者基因的異常在本文中也稱為“患者基因異常”，包括但不限於患者基因突變。患者靶基因的異常在本文中也稱為“患者靶基因異常”，包括但不限於患者靶基因突變。An abnormality in a target gene is also referred to herein as a "target gene abnormality" and includes, but is not limited to, a target gene mutation. Abnormalities in drug sensitivity genes, also referred to herein as "drug sensitivity abnormalities," include, but are not limited to, drug sensitivity mutations that sensitize cancer cells to anticancer drugs (eg, DNA damaging agents such as PARPi or ATRi). Abnormalities in drug resistance genes, also referred to herein as "drug resistance aberrations," include, but are not limited to, drug resistance mutations that render cancer cells resistant to anticancer drugs (eg, DNA damaging agents such as PARPi or ATRi). An abnormality in a patient's gene is also referred to herein as a "patient's genetic abnormality", including but not limited to a patient's gene mutation. An abnormality in a patient's target gene is also referred to herein as a "patient's target gene abnormality", including but not limited to a patient's target gene mutation.

基因異常的“狀態”可以指基因異常的存在或不存在，或基因的異常水準(表達或活性或修飾水準)。在一些實施方案中，與對照相比，一個或多個藥物敏感性基因中存在異常(例如突變)表明(a)所述個體更有可能對抗癌藥物治療產生應答或(b)選擇所述個體進行抗癌藥物(例如，DNA損傷劑，如PARPi或ATRi)治療。在一些實施方案中，與對照相比，一個或多個藥物敏感性基因不存在異常(例如突變)表明(a)所述個體不可對抗癌藥物(例如DNA損傷劑如PARPi或ATRi)的治療應答，或(b)不選擇所述個體進行抗癌藥物治療。在一些實施方案中，一個或多個藥物敏感性基因和/或一個或多個耐藥基因的異常水準(例如表達水準或活性水準或修飾水準)與個體對治療應答的可能性相關。例如，一個或多個藥物敏感性基因的水準(例如表達或活性或修飾水準)在降低或消除基因功能的方向上的較大偏差表明所述個體更有可能對抗癌藥物(例如，DNA損傷劑，如PARPi 或ATRi)治療產生應答。在一些實施方案中，基於一個或多個藥物敏感性基因和/或一個或多個耐藥基因的水準(例如表達水準或活性水準或修飾水準)的預測模型(例如綜合評分)用於預測(a)所述個體對抗癌藥物治療應答的可能性和(b)是否選擇個體進行抗癌藥物治療。在一些實施方案中，預測模型(包括例如每個水準的係數)可以藉由使用臨床試驗資料的統計分析例如回歸分析來獲得。The "status" of a genetic abnormality can refer to the presence or absence of a genetic abnormality, or the abnormal level (expression or activity or modification level) of a gene. In some embodiments, the presence of an abnormality (e.g., a mutation) in one or more drug sensitivity genes as compared to a control indicates (a) that the individual is more likely to respond to an anticancer drug treatment or (b) selects for the The individual is treated with an anticancer drug (eg, a DNA damaging agent such as PARPi or ATRi). In some embodiments, the absence of an abnormality (e.g., a mutation) in one or more drug sensitivity genes compared to a control indicates (a) that the individual is not treatable with an anticancer drug (e.g., a DNA damaging agent such as PARPi or ATRi) response, or (b) not selecting said individual for anticancer drug treatment. In some embodiments, abnormal levels (eg, levels of expression or levels of activity or levels of modification) of one or more drug sensitivity genes and/or one or more drug resistance genes correlate with the likelihood of an individual responding to treatment. For example, a greater deviation in the level (e.g., expression or activity or modification level) of one or more drug-sensitive genes in the direction of reducing or eliminating gene function indicates that the individual is more likely to have an anticancer drug (e.g., agents, such as PARPi or ATRi) treatment responds. In some embodiments, a predictive model (e.g., composite score) based on the level (e.g., expression level or activity level or modification level) of one or more drug sensitivity genes and/or one or more drug resistance genes is used to predict ( a) the likelihood that the individual will respond to anticancer drug treatment and (b) whether the individual is selected for anticancer drug treatment. In some embodiments, predictive models (including, for example, coefficients for each level) can be obtained by statistical analysis, such as regression analysis, using clinical trial data.

在一些實施方案中，偵測一種或多種藥物敏感性異常和/或耐藥異常包含偵測一個或多個藥物敏感性基因和/或一個或多個耐藥基因(或基因產物)中的突變，例如藉由基因組定序(DNA-SEQ)、轉錄組定序(RNA-SEQ)、質譜或任何其他核酸/肽序列偵測方法。在一些實施方案中，偵測一種或多種藥物敏感性異常和/或耐藥異常包括與對照水準例如藉由 qPCR、RNA-seq、質譜、蛋白質印跡或任何其他RNA或蛋白質表達水準偵測方法相比，偵測到一個或多個藥物敏感性基因和/或一個或多個藥物敏感性基因的異常(例如，降低或缺乏)表達(例如，RNA或蛋白質)。在一些實施方案中，偵測一種或多種藥物敏感性異常和/或耐藥異常包括與對照水準(例如，健康個體)相比，偵測到一個或多個藥物敏感性基因和/或一個或多個耐藥基因處的異常修飾，例如表觀遺傳修飾(例如，DNA甲基化、組蛋白甲基化、組蛋白乙醯化)或翻譯後修飾(例如，泛素化、磷酸化)。任何已知的用於偵測DNA、核小體、RNA 或蛋白質上修飾的方法都可以在本文中使用，例如染色質免疫共沉澱定序(ChIP-seq)、ChIP-qPCR、DNase-seq、MNase-seq、質譜、蛋白質印跡等。在一些實施方案中，與對照水準(例如，健康的個體)相比，偵測一種或多種藥物敏感性異常和/或耐藥異常包含偵測一個或多個藥物敏感性基因和/或一個或多個耐藥基因的表達產物(例如，RNA或蛋白質)(或其部分)的異常(例如，降低或缺失)活性。本文可以使用任何合適的基因功能/活性測試方法，例如偵測信號轉導、下游通路分子的啟動狀態(例如，磷酸化狀態)、蛋白-蛋白結合親和力和/或特異性、代謝、細胞行為(例如，細胞增殖、死亡、細胞週期)、細胞因數釋放等。In some embodiments, detecting one or more drug sensitivity abnormalities and/or drug resistance abnormalities comprises detecting mutations in one or more drug sensitivity genes and/or one or more drug resistance genes (or gene products) , eg by genome sequencing (DNA-SEQ), transcriptome sequencing (RNA-SEQ), mass spectrometry or any other nucleic acid/peptide sequence detection method. In some embodiments, detecting one or more drug susceptibility abnormalities and/or drug resistance abnormalities comprises comparing to control levels, e.g., by qPCR, RNA-seq, mass spectrometry, Western blot, or any other RNA or protein expression level detection method. Compared, one or more drug sensitivity genes and/or abnormal (eg, reduced or absent) expression (eg, RNA or protein) of one or more drug sensitivity genes is detected. In some embodiments, detecting one or more drug sensitivity abnormalities and/or drug resistance abnormalities comprises detecting one or more drug sensitivity genes and/or one or more drug sensitivity genes compared to control levels (eg, healthy individuals). Aberrant modifications at multiple resistance genes, such as epigenetic modifications (eg, DNA methylation, histone methylation, histone acetylation) or post-translational modifications (eg, ubiquitination, phosphorylation). Any known method for detecting modifications on DNA, nucleosomes, RNA or proteins can be used herein, such as chromatin immunoprecipitation sequencing (ChIP-seq), ChIP-qPCR, DNase-seq, MNase-seq, mass spectrometry, western blot, etc. In some embodiments, detecting one or more drug sensitivity abnormalities and/or drug resistance abnormalities compared to control levels (eg, healthy individuals) comprises detecting one or more drug sensitivity genes and/or one or more Abnormal (eg, reduced or absent) activity of expression products (eg, RNA or protein) (or parts thereof) of multiple drug-resistant genes. Any suitable assay for gene function/activity may be used herein, e.g., detection of signal transduction, initiation status (e.g., phosphorylation status) of downstream pathway molecules, protein-protein binding affinity and/or specificity, metabolism, cellular behavior ( For example, cell proliferation, death, cell cycle), cytokine release, etc.

綜合評分Overall rating

在一些實施方案中，可以使用業內已知的任何方法計算綜合評分，和/或可以選擇綜合評分閾值水準。例如，參見US20160369353中的反應分數或重組能力分數(RPS)，也參見US20200254259、US20180068083，它們各自的內容藉由引用以其整體併入本文。In some embodiments, the composite score can be calculated using any method known in the art, and/or a composite score threshold level can be selected. For example, see Reaction Score or Recombinability Score (RPS) in US20160369353, see also US20200254259, US20180068083, the contents of each of which are hereby incorporated by reference in their entirety.

在一些實施方案中，綜合評分基於一種或多種藥物敏感性異常和/或耐藥異常，例如一種或多種藥物敏感性突變、耐藥突變、藥物敏感性基因的異常表達、耐藥基因的異常表達、藥物敏感性基因表達產物的異常活性、耐藥基因表達產物的異常活性、藥物敏感性基因(或基因產物)的異常修飾、耐藥基因(或基因產物)的異常修飾等。在一些實施方案中，綜合評分是藉由從(患者攜帶的具有藥物敏感性異常的藥物敏感性基因的數量)中減去(患者攜帶的具有耐藥異常的耐藥基因的數量)獲得的，其中如果綜合評分高於零則個體被選擇進行治療。在一些實施方案中，患者中藥物敏感性突變或耐藥突變的嚴重程度增加了綜合評分的權重，例如，與影響相同藥物敏感性基因的表達和/或活性較小的另一個藥物敏感性突變相比，影響藥物敏感性基因的表達和/或活性的藥物敏感性突變更多地增加了綜合評分的權重。在一些實施方案中，與對照水準(例如，健康個體)相比，患者中藥物敏感性基因或耐藥基因的異常表達程度增加了綜合評分的權重，例如，與相同藥物敏感性基因的表達降低相比，藥物敏感性基因的表達缺失增加了綜合評分的權重。在一些實施方案中，與對照水準(例如，健康個體)相比，患者中藥物敏感性基因或耐藥基因的異常活性(例如，RNA或蛋白質活性)的程度增加了綜合評分的權重，例如，與相同藥物敏感性基因的蛋白質活性降低(例如，結合減少)相比，藥物敏感性基因的蛋白質活性喪失(例如，結合被取消)增加了綜合評分的權重。在一些實施方案中，與對照水準(例如，健康個體)相比，患者中藥物敏感性基因或耐藥基因的異常修飾(例如，DNA、核小體、RNA或蛋白質的修飾)的程度增加了綜合評分的權重，例如，與相同藥物敏感性基因的蛋白質磷酸化降低相比，藥物敏感性基因的蛋白質磷酸化喪失(例如，信號轉導消失)給綜合評分增加了更多的權重。在一些實施方案中，每個耐藥基因具有抗性分數，並且每個藥物敏感性基因具有敏感性分數(例如，基於實驗、出版物或資料庫)。在一些實施方案中，綜合評分是藉由從(藥物敏感性基因的敏感性評分總和的絕對值)中減去(耐藥基因的耐藥評分總和的絕對值)獲得的，其中如果綜合評分高於零，則個體被選擇治療。In some embodiments, the composite score is based on one or more drug sensitivity abnormalities and/or drug resistance abnormalities, such as one or more drug sensitivity mutations, drug resistance mutations, aberrant expression of drug sensitivity genes, aberrant expression of drug resistance genes , Abnormal activity of drug-sensitive gene expression products, abnormal activity of drug-resistant gene expression products, abnormal modification of drug-sensitive genes (or gene products), abnormal modification of drug-resistant genes (or gene products), etc. In some embodiments, the composite score is obtained by subtracting (the number of drug resistance genes with drug resistance abnormalities carried by the patient) from (the number of drug sensitivity genes with drug sensitivity abnormalities carried by the patient), Wherein an individual is selected for treatment if the composite score is higher than zero. In some embodiments, the severity of a drug sensitivity or resistance mutation in a patient adds weight to the composite score, e.g., compared to another drug sensitivity mutation that affects expression and/or activity of the same drug sensitivity gene less Drug-sensitivity mutations that affect the expression and/or activity of drug-sensitivity genes added more weight to the composite score than . In some embodiments, the degree of aberrant expression of a drug sensitivity or resistance gene in a patient increases the weight of the composite score compared to control levels (e.g., healthy individuals), e.g., with reduced expression of the same drug sensitivity gene In contrast, loss of expression of drug susceptibility genes increased the weight of the composite score. In some embodiments, the degree of aberrant activity (e.g., RNA or protein activity) of a drug sensitivity gene or drug resistance gene in a patient compared to a control level (e.g., a healthy individual) increases the weight of the composite score, e.g., Loss of protein activity (eg, abolished binding) of a drug-sensitive gene adds weight to the composite score compared to reduced protein activity (eg, reduced binding) of the same drug-sensitive gene. In some embodiments, the degree of aberrant modification (e.g., modification of DNA, nucleosomes, RNA, or protein) of a drug sensitivity gene or drug resistance gene is increased in a patient compared to a control level (e.g., a healthy individual) Weighting of the composite score, for example, loss of protein phosphorylation (eg, loss of signal transduction) of a drug sensitivity gene adds more weight to the composite score than loss of protein phosphorylation of the same drug sensitivity gene. In some embodiments, each drug resistance gene has a resistance score and each drug sensitivity gene has a sensitivity score (eg, based on experiments, publications, or databases). In some embodiments, the composite score is obtained by subtracting (the absolute value of the sum of the resistance scores of the drug resistance genes) from (the absolute value of the sum of the sensitivity scores of the drug-sensitive genes), wherein if the composite score is high is less than zero, the individual is selected for treatment.

在一些實施方案中，對於特定的癌症類型(例如結直腸癌)和/或特定的抗癌藥物(例如，DNA損傷劑，例如PARPi或ATRi)，參數“m”是耐藥基因的總數，並且本文所述的藥物敏感性基因(以下也稱為“本文所述的基因小組”)。例如，在一些實施方案中，對於用於治療結直腸癌的DNA損傷劑，參數“m”是表1中提供的藥物敏感性基因和表5中提供的耐藥基因的總數(“基因組1”)。在一些實施方案中，對於用於治療結直腸癌的DNA損傷劑，參數“m”是表1中提供的藥物敏感性基因和表6中提供的耐藥基因的總數(“基因小組2”)。在一些實施方案中，對於用於治療結直腸癌的DNA損傷劑，參數“m”是表2中提供的藥物敏感性基因和表6中提供的耐藥基因的總數(“基因小組3”)。在一些實施方案中，對於用於治療結直腸癌的PARPi，參數“m”是表3中提供的藥物敏感性基因和表7中提供的耐藥基因的總數(“基因小組4”)。在一些實施方案中，對於用於治療結直腸癌的ATRi，參數“m”是表4中提供的藥物敏感性基因和表8中提供的耐藥基因的總數(“基因小組5”)。在一些實施方案中，對於用於治療結直腸癌的PARPi，參數“m”是表A中提供的藥物敏感性基因和表B中提供的耐藥基因的總數(“基因小組6”)。在一些實施方案中，來自所述個體樣本的一種或多種患者異常(例如，突變或異常表達/活性/修飾)，例如一種或多種患者突變(例如，非同義、無義、錯義、移碼、插入、缺失、終止性丟失、終止性獲得、導致錯誤剪接的突變、基因融合等)在屬於本文所述基因小組或屬於基因小組1、基因小組2、基因小組3、基因小組4、基因小組5、或基因小組6的一種或多種患者基因中進行鑒定。在一些實施方案中，從個體樣本中，在屬於本文所述基因小組或屬於基因小組1、或基因小組2或基因小組3、或基因小組4、或基因小組 5、或基因小組 6的患者基因中未鑒定出患者異常(例如，患者突變)。從屬於本文所述基因小組或屬於基因小組1、或基因小組2、或基因小組3、或基因小組4、或基因小組5、或基因小組6的患者(例如，藉由NGS的患者樣本)鑒定的患者基因或患者異常(例如，突變或異常表達/活性/修飾)，在下文中也分別稱為“患者靶基因”或“患者靶異常” (例如“患者靶突變”)。參數“m”是至少為1的整數，並且是針對特定癌症類型和特定抗癌藥物的常數。In some embodiments, the parameter "m" is the total number of drug resistance genes for a particular cancer type (e.g., colorectal cancer) and/or a particular anticancer drug (e.g., a DNA damaging agent such as PARPi or ATRi), and The drug sensitivity genes described herein (hereinafter also referred to as "the gene panel described herein"). For example, in some embodiments, for DNA damaging agents used in the treatment of colorectal cancer, the parameter "m" is the total number of drug-sensitive genes provided in Table 1 and drug-resistant genes provided in Table 5 ("genome 1" ). In some embodiments, for a DNA damaging agent for the treatment of colorectal cancer, the parameter "m" is the total number of drug sensitivity genes provided in Table 1 and drug resistance genes provided in Table 6 ("Gene Panel 2") . In some embodiments, for a DNA damaging agent for the treatment of colorectal cancer, the parameter "m" is the total number of drug sensitivity genes provided in Table 2 and drug resistance genes provided in Table 6 ("Gene Panel 3") . In some embodiments, for PARPi for the treatment of colorectal cancer, the parameter "m" is the total number of drug sensitivity genes provided in Table 3 and drug resistance genes provided in Table 7 ("Gene Panel 4"). In some embodiments, for an ATRi for the treatment of colorectal cancer, the parameter "m" is the total number of drug sensitivity genes provided in Table 4 and drug resistance genes provided in Table 8 ("Gene Panel 5"). In some embodiments, for PARPi for the treatment of colorectal cancer, the parameter "m" is the total number of drug sensitivity genes provided in Table A and drug resistance genes provided in Table B ("Gene Panel 6"). In some embodiments, one or more patient abnormalities (e.g., mutations or aberrant expression/activity/modifications) from the individual sample, such as one or more patient mutations (e.g., nonsynonymous, nonsense, missense, frameshift , insertion, deletion, terminating loss, terminating gain, mutation leading to missplicing, gene fusion, etc.) 5, or one or more patient genes of gene panel 6 are identified. In some embodiments, from an individual sample, in the patient's gene group that belongs to the gene group described herein or belongs to the gene group 1, or the gene group 2 or the gene group 3, or the gene group 4, or the gene group 5, or the gene group 6 No patient abnormalities (eg, patient mutations) were identified in . Identification of patients belonging to a genogroup described herein or belonging to genopanel 1, or genopanel 2, or genopanel 3, or genopanel 4, or genopanel 5, or genopanel 6 (e.g., from a patient sample by NGS) The patient gene or patient abnormality (for example, mutation or abnormal expression/activity/modification), is also referred to as "patient target gene" or "patient target abnormality" (for example, "patient target mutation"), respectively, hereinafter. The parameter "m" is an integer of at least 1 and is a constant for a particular cancer type and a particular anticancer drug.

在一些實施方案中，綜合評分是基於一個或多個患者相關參數計算得出的，例如i)從患者中鑒定的各個患者靶基因(例如，藉由NGS)攜帶的有害突變(例如，非同義、無義、錯義、移碼、插入、缺失、終止性丟失、導致錯誤剪接的突變、基因融合等)的數量(參數“n”)，ii)從患者中鑒定(例如，藉由NGS)的在特定患者靶基因上攜帶特定有害突變的細胞的估算分數(estimated fraction，參數“

Figure 02_image007
”) iii)患者疾病組織與正常組織中患者靶基因表達水準的對數尺度(例如，log2)的倍數變化(參數“LFC”)等。在一些實施方案中，所述一種或多種患者相關參數是基於來自患者樣本的資料/資訊，例如定序讀數計數得出的。參數“
Figure 02_image009
”表示在從患者中鑒定的第i個患者靶基因中攜帶第j個突變的細胞的估算分數。0 ＜
Figure 02_image009
≤ 1。“n”是至少為1的整數，並且是相應識別的在患者靶基因中偵測到的有害患者靶突變的總數。“j”為整數，並且1≤j≤n。“i”為整數，並且0≤i≤m。當i = 0時，表示從個體樣本中，在屬於本文所述的基因小組、或屬於基因小組1、或基因小組2、或基因小組3、或基因小組4、或基因小組5或基因小組6的任何患者基因中未鑒定出有害突變。在一些實施方案中，基於在從患者樣本中鑒定的第i個患者靶基因中包含突變的所有序列中包含第j個突變的序列的分數來估算在第i個患者靶基因中攜帶第j個突變的細胞分數。參數“LFCi”表示患者疾病組織與正常組織中第i個患者靶基因的表達水準的對數尺度(例如，log2)的倍數變化。可以使用任何已知方法量測患者靶基因的表達水準，例如 RNA-seq、qPCR、質譜、蛋白質印跡、FISH、免疫螢光染色等。 In some embodiments, the composite score is calculated based on one or more patient-related parameters, such as i) deleterious mutations (e.g., non-synonymous , nonsense, missense, frameshifts, insertions, deletions, terminating losses, mutations leading to missplicing, gene fusions, etc.) (parameter "n"), ii) identified from patients (e.g., by NGS) The estimated fraction of cells carrying a specific deleterious mutation on a specific patient target gene (estimated fraction, parameter "
Figure 02_image007
”) iii) fold change in the logarithmic scale (e.g., log2) of the expression level of the patient's target gene in the patient's disease tissue versus normal tissue (parameter "LFC"), etc. In some embodiments, the one or more patient-related parameters are Based on data/information from patient samples, such as sequenced read counts. Parameters"
Figure 02_image009
" represents the estimated fraction of cells carrying the jth mutation in the ith patient target gene identified from the patient. 0 <
Figure 02_image009
≤ 1. "n" is an integer of at least 1 and is the total number of correspondingly identified deleterious patient target mutations detected in the patient target gene. "j" is an integer, and 1≤j≤n. "i" is an integer, and 0≤i≤m. When i = 0, it means that from the individual sample, in the gene group described herein, or in gene group 1, or gene group 2, or gene group 3, or gene group 4, or gene group 5 or gene group 6 No deleterious mutations were identified in any of the patient genes. In some embodiments, the number of sequences carrying the jth mutation in the ith patient target gene is estimated based on the fraction of all sequences comprising the mutation in the ith patient target gene identified from the patient sample. Mutant cell fraction. The parameter "LFCi" represents the fold change on a logarithmic scale (eg, log2) of the expression level of the ith patient target gene in the patient's diseased tissue versus normal tissue. The expression level of the target gene in the patient can be measured using any known method, such as RNA-seq, qPCR, mass spectrometry, Western blot, FISH, immunofluorescent staining, and the like.

在一些實施方案中，綜合評分基於一個或多個基因相關參數計算，例如i)患者靶基因和抗癌藥物治療之間的相關性(正相關或負相關)(例如，IC50) (參數“r”)，它源自機器學習(例如，基於來自細胞株公共資料的訓練模型)，ii)患者靶基因對抗癌藥物治療應答的準則化權重(參數“

Figure 02_image013
”)，它源自機器學習(例如，基於來自細胞株公共資料的訓練模型)，iii)患者靶基因有害突變的預測影響(參數“η”；例如，基於使用公共資料庫進行危害性預測，例如異常基因或基因產物活性)，iv)根據Kaplan-Meier生存曲線(參數“
Figure 02_image016
”；例如，基於癌症基因組圖譜(TCGA)資料庫和/或 cBioPortal資料庫)，在給定時間點，患者靶基因的淨生存貢獻與總生存的比率，v) 患者靶基因在疾病組織相對正常組織中表達水準（例如，基於患者資料庫，即從患有相同癌症的患者那裡收集的資訊)的對數尺度(例如 log2)的倍數變化(參數“LFC”)等。在一些實施方案中，一個或多個基因相關參數是基於公共或患者資料庫中的資料匯出的，用於訓練綜合評分模型。 參數“
Figure 02_image018
”表示從患者中鑒定的第i個患者靶基因與抗癌藥物治療(例如IC50)之間的相關性(正相關或負相關)，該相關性源自機器學習。參數“
Figure 02_image021
”表示第i個患者靶基因回應抗癌藥物治療的歸一化權重(即第i個患者靶基因的功能喪失對抗癌藥物治療的貢獻)，其源自機器學習。參數“
Figure 02_image024
”表示第i個患者靶基因的第j個有害突變的預測影響(例如，基於公共資料庫的危害性預測，或者為手動分配的常數)。 參數“
Figure 02_image027
”表示根據 Kaplan-Meier 生存曲線(例如，基於TCGA和/或cBioPortal資料庫)在給定時間點第i個患者靶基因的淨生存貢獻與總生存的比率。參數“
Figure 02_image029
”表示疾病組織與正常組織中第i個患者靶基因的表達水準的對數尺度(例如 log2)的倍數變化(例如，基於患者資料庫，即從患有相同癌症的患者那裡收集的資訊)。“i”為整數，並且0≤i≤m。“j”為整數，並且1≤j≤n。 In some embodiments, the composite score is calculated based on one or more gene-related parameters, e.g., i) the correlation (positive or negative) (e.g., IC50) between a patient's target gene and anticancer drug treatment (parameter "r ”), which is derived from machine learning (e.g., based on a trained model from public data on cell lines), ii) normalized weights of the patient’s target gene response to anticancer drug treatment (parameter “
Figure 02_image013
”) derived from machine learning (e.g., based on a trained model from public data on cell lines), iii) the predicted impact of a deleterious mutation in a patient’s target gene (parameter “η”; e.g., based on hazard prediction using a public data base, such as abnormal gene or gene product activity), iv) according to the Kaplan-Meier survival curve (parameter "
Figure 02_image016
”; e.g., based on The Cancer Genome Atlas (TCGA) database and/or cBioPortal database), at a given time point, the ratio of the net survival contribution of the patient's target gene to overall survival, v) the patient's target gene is relatively normal in disease tissue Fold change on a logarithmic scale (e.g. log2) of expression levels in tissues (e.g., based on patient databases, i.e., information collected from patients with the same cancer) (parameter "LFC"), etc. In some embodiments, a or multiple gene-related parameters are exported based on data in public or patient databases for training a comprehensive scoring model. Parameters"
Figure 02_image018
"Denotes the correlation (positive or negative) between the i-th patient target gene identified from a patient and an anticancer drug treatment (e.g. IC50) derived from machine learning. Parameter"
Figure 02_image021
"Represents the normalized weight of the i-th patient's target gene response to anti-cancer drug treatment (ie, the contribution of the loss-of-function of the i-th patient's target gene to anti-cancer drug treatment), which is derived from machine learning. Parameter"
Figure 02_image024
"Represents the predicted impact of the jth deleterious mutation in the i'th patient's target gene (e.g., based on public database hazard predictions, or as a manually assigned constant). Parameters"
Figure 02_image027
"Represents the ratio of the net survival contribution of the i-th patient's target gene to overall survival at a given time point according to a Kaplan-Meier survival curve (eg, based on TCGA and/or the cBioPortal database). Parameter"
Figure 02_image029
"Represents the fold change on a logarithmic scale (e.g. log2) of the expression level of the ith patient's target gene in disease tissue versus normal tissue (e.g., based on a patient database, i.e., information collected from patients with the same cancer)."i" is an integer, and 0≤i≤m. "j" is an integer, and 1≤j≤n.

在一些實施方案中，綜合評分是基於一個或多個通路相關參數計算的，例如i)患者靶基因在涉及患者靶基因的通路和/或調節網路中的估計權重(參數“

Figure 02_image031
”；例如，基於公共資料庫(如 KEGG和InterProScan)，ii) 患者靶基因在抗癌藥物相關通路中的歸一化權重(參數“ψ”；例如，基於公共資料庫)等；在一些實施方案中，一個或多個通路相關參數是基於公共資料庫中的資料匯出的，用於訓練綜合評分模型。 參數“
Figure 02_image033
”表示涉及第i個患者靶基因的通路和/或調控網路中第i個患者靶基因的估計權重(例如，基於公共資料庫，如KEGG和InterProScan)。 參數“
Figure 02_image035
”表示抗癌藥物相關通路中第i個患者靶基因的歸一化權重，例如，基於公共資料庫。“i”為整數，並且0≤i≤m。 In some embodiments, the composite score is calculated based on one or more pathway-related parameters, such as i) the estimated weight of the patient's target gene in pathways and/or regulatory networks involving the patient's target gene (parameter "
Figure 02_image031
”; e.g., based on public databases (such as KEGG and InterProScan), ii) normalized weights of patient target genes in anticancer drug-related pathways (parameter “ψ”; e.g., based on public databases); etc.; in some implementations In the scheme, one or more pathway-related parameters are exported based on data in public databases and used to train a comprehensive scoring model. Parameters"
Figure 02_image033
"Denotes the estimated weight of the i-th patient target gene in the pathway and/or regulatory network involving the i-th patient target gene (e.g., based on public databases such as KEGG and InterProScan). Parameters"
Figure 02_image035
" denotes the normalized weight of the i-th patient's target gene in an anticancer drug-related pathway, eg, based on a public database. "i" is an integer, and 0≤i≤m.

在一些實施方案中，基於選自本文所述的患者相關參數、基因相關參數和通路相關參數中的一項或多項的一個或多個參數計算綜合評分。In some embodiments, a composite score is calculated based on one or more parameters selected from one or more of the patient-related parameters, gene-related parameters, and pathway-related parameters described herein.

在一些實施方案中，綜合評分使用公式I計算：In some embodiments, the composite score is calculated using Formula I:

綜合評分=

Figure 02_image037
Overall Rating =
Figure 02_image037

其中in

a、b和c是模型校正的常數(例如，相應抗癌藥的訓練模型得到的常數)，其中-1≤a≤1，-1≤b≤1，-1≤c≤1；a, b, and c are constants for model correction (for example, constants obtained by training models of corresponding anticancer drugs), where -1≤a≤1, -1≤b≤1, -1≤c≤1;

m是本文描述的基因小組(例如基因小組1-6中的任一個)中的耐藥基因和藥物敏感性基因的總數；m is the total number of drug resistance genes and drug sensitivity genes in a gene panel described herein (eg, any of gene panels 1-6);

n是在患者的第i個患者靶基因上偵測到的有害突變的數量；n is the number of deleterious mutations detected on the ith patient target gene in the patient;

“

Figure 02_image039
”是在第i個患者靶基因中攜帶第j個有害突變的患者細胞的估算分數，其中0 ＜
Figure 02_image039
≤ 1； "
Figure 02_image039
” is the estimated fraction of patient cells carrying the jth deleterious mutation in the ith patient’s target gene, where 0 <
Figure 02_image039
≤ 1;

Figure 02_image042
是第i個患者靶基因與抗癌藥物治療(例如IC50)之間的相關性(正相關或負相關)；
Figure 02_image042
is the correlation (positive or negative correlation) between the i-th patient's target gene and anticancer drug treatment (eg, IC50);

Figure 02_image044
是第i個患者靶基因響應抗癌藥物治療的歸一化權重；
Figure 02_image044
is the normalized weight of the i-th patient's target gene response to anticancer drug treatment;

Figure 02_image046
是第i個患者靶基因的第j個有害突變的預測影響；
Figure 02_image046
is the predicted impact of the jth deleterious mutation in the target gene of the ith patient;

Figure 02_image048
是根據Kaplan-Meier生存曲線在給定時間點第i個患者靶基因的淨生存貢獻與總生存的比率；
Figure 02_image048
is the ratio of the net survival contribution of the i-th patient's target gene to overall survival at a given time point according to the Kaplan-Meier survival curve;

Figure 02_image050
是疾病組織與正常組織中第i個患者靶基因表達水準在對數尺度(例如，log2)的倍數變化；
Figure 02_image050
is the fold change of the i-th patient's target gene expression level on a logarithmic scale (for example, log2) between disease tissue and normal tissue;

Figure 02_image052
是涉及第i個患者靶基因的通路和/或調控網路中第i個患者靶基因的估計權重；
Figure 02_image052
is the estimated weight of the i-th patient target gene in the pathway and/or regulatory network involving the i-th patient target gene;

Figure 02_image054
是抗癌藥物相關通路中第i個患者靶基因的歸一化權重；
Figure 02_image054
is the normalized weight of the i-th patient target gene in the anticancer drug-related pathway;

其中i和j均為整數，0≤i≤m，1≤j≤n；和where i and j are both integers, 0≤i≤m, 1≤j≤n; and

Figure 02_image056
是
Figure 02_image050
的準則分數(“Z-分數”)：
Figure 02_image056
yes
Figure 02_image050
The guideline score ("Z-score") for :

Figure 02_image058
Figure 02_image058

其中

Figure 02_image060
是疾病組織與正常組織中第i個患者靶基因表達水準在對數尺度(例如 log2)的倍數變化的中位數(例如，基於患者資料庫，即從具有相同癌症的患者收集的資訊);和 in
Figure 02_image060
is the median of the fold change in the i-th patient's target gene expression level on a logarithmic scale (e.g., log2) between diseased tissue and normal tissue (e.g., based on a patient database, i.e., information collected from patients with the same cancer); and

其中

Figure 02_image063
是疾病組織與正常組織中第i個患者靶基因的表達水準在對數尺度(例如log2)的倍數變化的準則差(例如，基於患者資料庫，即從患有相同癌症的患者收集的資訊)。 in
Figure 02_image063
is the criterion difference of the fold change in the expression level of the i-th patient's target gene on a logarithmic scale (eg, log2) between diseased tissue and normal tissue (eg, based on a patient database, ie, information collected from patients with the same cancer).

在一些實施方案中，綜合評分閾值水準是0。在一些實施方案中，如果根據式I的患者的綜合評分高於0，則患者適合(即，可獲益於)抗癌藥物(例如，DNA損傷劑，如PARPi或ATRi)治療。在一些實施方案中，如果根據式I的患者的綜合評分高於或等於至少0.1(例如，0.3)，則選擇或推薦患者進行抗癌藥物治療。在一些實施方案中，如果根據式I的患者的綜合評分大於0但小於0.1，則患者適合抗癌藥物治療，但應使用其他方法(例如，藥物劑量測試、癌症基因測試(例如，尋找可能有助於抗癌藥物治療的額外協同突變，或核實原發癌症類型)等)或基於其他資訊(例如，患者的臨床記錄或已知耐藥性等)來確定是否應選擇或推薦患者進行抗癌藥物治療。在一些實施方案中，如果根據式I的患者的綜合評分低於或等於0，則患者不適合(即，不可獲益於)或被排除在抗癌藥物治療之外。在一些實施方案中，在完全排除患者接受抗癌藥物治療之前，如果根據式 I 的患者的綜合評分等於 0，或非常接近 0(例如，-0.1 至 0)，應使用其他方法(例如，藥物劑量測試、癌症基因測試(例如，尋找可能有助於抗癌藥物治療的額外協同突變，或核實原發性癌症類型)等)或基於其他資訊(例如，患者的臨床記錄或已知的耐藥性等)進行進一步評估。In some embodiments, the composite score threshold level is zero. In some embodiments, a patient is suitable for (ie, would benefit from) treatment with an anticancer drug (eg, a DNA damaging agent such as PARPi or ATRi) if the patient's composite score according to Formula I is above 0. In some embodiments, a patient is selected or recommended for anticancer drug treatment if the patient's composite score according to Formula I is greater than or equal to at least 0.1 (eg, 0.3). In some embodiments, if the patient's composite score according to Formula I is greater than 0 but less than 0.1, the patient is suitable for anticancer drug therapy, but other methods (e.g., drug dosage testing, cancer genetic testing (e.g., looking for possible additional co-mutations that may contribute to anticancer drug therapy, or to verify the primary cancer type), etc.) or based on other information (e.g., the patient's clinical record or known drug resistance, etc.) to determine whether a patient should be selected or recommended for anticancer medical treatement. In some embodiments, if the patient's composite score according to Formula I is less than or equal to 0, the patient is not suitable (ie, does not benefit from) or is excluded from anticancer drug treatment. In some embodiments, other methods (eg, drug Dose testing, cancer genetic testing (e.g., to look for additional synergistic mutations that may contribute to anticancer drug therapy, or to verify primary cancer type), etc.) or based on other information (e.g., patient's clinical record or known drug resistance etc.) for further evaluation.

在一些實施方案中，所述方法進一步包含選擇性地增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B,例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含選擇性增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含在個體樣本中選擇性增濃一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。In some embodiments, the method further comprises selectively enriching the individual sample in one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), For example a drug susceptibility gene selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB , POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2 , BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4 , UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8 , CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1 , EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2 , NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB TP53BP1 , LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF2 3. PEG3 , INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10 , MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, for example, using reagents known in the art or provided herein, such as described herein Baits, probes, capture molecules or oligonucleotides to generate enriched samples. In some embodiments, the method further comprises selectively enriching one or more nucleic acids or polypeptides comprising or encoded by one or more drug resistance genes (or portions thereof), such as selected Drug resistance genes from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、 CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1 , SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, for example , using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein, to generate enriched samples. In some embodiments, the method further comprises selectively enriching in the individual sample one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), e.g. A drug sensitivity gene selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP 53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and comprise or are encoded by one or more drug resistance genes (or portions thereof), such as A drug resistance gene selected from the group consisting of PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA , RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A , IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11 , INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC , CREBBP, RELA, E2F3, ITIH6, BRPF3, Anapc7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MyH14, RASL10B, MyH9, FGF19, EIF4E2, CUL9, CDC25A, KMT2 D, Foxg1, Arid1a, CIR1, TSC1, SMAD2 , CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3 , THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1 , E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNB IP1, SCN3A , DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, For example, an enriched sample is generated using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein.

在一些實施方案中，所述方法進一步包含選擇性地增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。In some embodiments, the method further comprises selectively enriching the individual sample in one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), For example a drug susceptibility gene selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB , POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2 , BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4 , UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8 , CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1 , EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2 , NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB TP53BP1 , LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF2 3. PEG3 , INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10 , MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and comprise or be encoded by one or more drug resistance genes (or portions thereof), For example, a drug resistance gene selected from the group consisting of RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, for example, using reagents known in the art or provided herein, such as the baits, probes, Capture molecules or oligonucleotides are used to generate enriched samples.

在一些實施方案中，所述方法進一步包含在個體中選擇性增濃樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含選擇性增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含在個體樣本中選擇性增濃一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：GSK3A、STAG1、YLPM1、NBN、PTEN、MYO9B、ATR、SMAD7、HDAC2、NFE2L1、POLQ、GSK3B、DNTTIP1、CHD7、ZFHX3、DSCAM、KDM5C、PRKAA1、ABCC1、GFRA1、WEE1、FBXW7、CDK2、ACTA1、FBXW11、MGA、BAZ1A、ATM、YWHAE、和FANCM，和包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：RPTOR、TP53、ID1、MYH9、RHEB、SETD2、SMAD4、CHP1、RAPGEF1、RAF1、IKBKG、IGF1R、RICTOR、MYC、GNA11、PIK3R2、CRKL、PRKAR1A、E2F3、MLST8、ACVRL1、AKT1、MAPK1、MED12、PSENEN、VAV1、CTNNB1、EPOR、SRC、PIK3CA、CHD2、PARP1、和EIF4B，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。In some embodiments, the method further comprises selectively enriching in the individual one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof) in the sample , such as a drug sensitivity gene selected from the group consisting of GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, for example, using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligos described herein Nucleotides to generate enriched samples. In some embodiments, the method further comprises selectively enriching one or more nucleic acids or polypeptides comprising or encoded by one or more drug resistance genes (or portions thereof), such as selected Drug resistance genes from the following groups: RPTOR, TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1, CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, e.g., using reagents known in the art or provided herein, e.g., baits, probes, capture molecules described herein or oligonucleotides to generate enriched samples. In some embodiments, the method further comprises selectively enriching in the individual sample one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), e.g. A drug sensitivity gene selected from the group consisting of GSK3A, STAG1, YLPM1, NBN, PTEN, MYO9B, ATR, SMAD7, HDAC2, NFE2L1, POLQ, GSK3B, DNTTIP1, CHD7, ZFHX3, DSCAM, KDM5C, PRKAA1, ABCC1, GFRA1, WEE1, FBXW7, CDK2, ACTA1, FBXW11, MGA, BAZ1A, ATM, YWHAE, and FANCM, and comprise or be encoded by one or more drug resistance genes (or parts thereof), such as selected from the group consisting of: RPTOR , TP53, ID1, MYH9, RHEB, SETD2, SMAD4, CHP1, RAPGEF1, RAF1, IKBKG, IGF1R, RICTOR, MYC, GNA11, PIK3R2, CRKL, PRKAR1A, E2F3, MLST8, ACVRL1, AKT1, MAPK1, MED12, PSENEN, VAV1 , CTNNB1, EPOR, SRC, PIK3CA, CHD2, PARP1, and EIF4B, e.g., using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein, to generate enrichment of samples.

在一些實施方案中，所述方法還包括選擇性地增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1,例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含在個體樣本中選擇性增濃一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX,例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含選擇性增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含選擇性增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含在個體樣本中選擇性增濃一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含在個體樣本中選擇性增濃一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。In some embodiments, the method further comprises selectively enriching the individual sample in one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), For example a drug susceptibility gene selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB , POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2 , BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4 , UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8 , CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, e.g., using reagents known in the art or provided herein , such as baits, probes, capture molecules or oligonucleotides described herein to generate enriched samples. In some embodiments, the method further comprises selectively enriching in the individual sample one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), e.g. A drug sensitivity gene selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, for example, using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein, to generate enriched samples. In some embodiments, the method further comprises selectively enriching one or more nucleic acids or polypeptides comprising or encoded by one or more drug resistance genes (or portions thereof), such as selected Drug resistance genes from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, for example, using Reagents such as baits, probes, capture molecules or oligonucleotides described herein are provided to generate an enriched sample. In some embodiments, the method further comprises selectively enriching one or more nucleic acids or polypeptides comprising or encoded by one or more drug resistance genes (or portions thereof), such as selected Drug resistance genes from the following group: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1 For example, an enriched sample is generated using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein. In some embodiments, the method further comprises selectively enriching in the individual sample one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), e.g. A drug sensitivity gene selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and contain or consist of one or more drug resistance genes (or Its part) codes, for example is selected from the resistance gene of following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B , ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2 , PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300 , EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1 , CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, for example, Enriched samples are generated using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein. In some embodiments, the method further comprises selectively enriching in the individual sample one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), e.g. A drug sensitivity gene selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and comprise or be encoded by one or more drug resistance genes (or parts thereof), such as drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1 , Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A , CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1, for example, using reagents known in the art or provided herein, such as baits, probes, capture molecules or Oligonucleotides to generate enriched samples.

在一些實施方案中，所述方法進一步包含選擇性增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含一個或多個藥物敏感性基因(或其部分)或由其編碼，例如選自下組的藥物敏感性基因：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B,例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含選擇性增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。在一些實施方案中，所述方法進一步包含選擇性增濃個體樣本中的一種或多種核酸或多肽，所述核酸或多肽包含或由一個或多個藥物敏感性基因(或其部分)編碼，例如選自下組的藥物敏感性基因：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和包含或由一個或多個耐藥基因(或其部分)編碼，例如選自下組的耐藥基因：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1，例如，使用業內已知的或本文提供的試劑，例如本文所述的誘餌、探針、捕獲分子或寡核苷酸來產生增濃的樣本。In some embodiments, the method further comprises selectively enriching in the individual sample one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), For example, a drug sensitivity gene selected from the group consisting of: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF , LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3 , TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7 , TCF7L2, CSNK1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, Anapc7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRRIQ1, LRRRIQ1 , STA1, ZFHX3, NALCN, MRGBP, MYO9B , HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7 , ZNF568 , FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1 , UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, for example, using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein, to generate enrichment of samples. In some embodiments, the method further comprises selectively enriching one or more nucleic acids or polypeptides comprising or encoded by one or more drug resistance genes (or portions thereof), such as selected Drug resistance genes from the following groups: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2 , RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, for example, using reagents known in the art or provided herein, such as described herein baits, probes, capture molecules or oligonucleotides to generate enriched samples. In some embodiments, the method further comprises selectively enriching the individual sample in one or more nucleic acids or polypeptides comprising or encoded by one or more drug susceptibility genes (or portions thereof), e.g. A drug sensitivity gene selected from the group consisting of ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, Z NF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and comprise or be encoded by one or more drug resistance genes (or parts thereof), such as drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2 , TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3 , PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R , MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1 , SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KiAA12 17 , MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B , FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1, for example, using reagents known in the art or provided herein, such as baits, probes, capture molecules or oligonucleotides described herein to generate Concentrated samples.

在一些實施方案中，選擇性增濃包含：(a)將誘餌與樣本組合，從而使誘餌與樣本中的一種或多種核酸雜交並產生核酸雜交體；和(b)單離核酸雜交體以產生增濃樣本。在一些實施方案中，選擇性增濃包含使用PCR擴增樣本中的一種或多種核酸以產生增濃樣本。在一些實施方案中，所述方法進一步包含對增濃樣本中的一種或多種核酸分子或其相關部分(例如已知含有突變的核酸片段)進行定序。在一些實施方案中，選擇性增濃包含：(a)將誘餌(例如抗體)與樣本結合，從而將誘餌與樣本中的一種或多種多肽結合並產生誘餌-多肽複合物；和(b)單離誘餌-多肽複合物以產生增濃樣本。In some embodiments, selective enrichment comprises: (a) combining the bait with the sample, such that the bait hybridizes to one or more nucleic acids in the sample and generates a nucleic acid hybrid; and (b) isolating the nucleic acid hybrid to generate Concentrate the sample. In some embodiments, selectively enriching comprises using PCR to amplify one or more nucleic acids in the sample to produce an enriched sample. In some embodiments, the method further comprises sequencing one or more nucleic acid molecules or related portions thereof (eg, nucleic acid fragments known to contain mutations) in the enriched sample. In some embodiments, selective enrichment comprises: (a) binding a bait (e.g., an antibody) to a sample, thereby binding the bait to one or more polypeptides in the sample and generating a bait-polypeptide complex; and (b) singly The bait-peptide complex is isolated to generate an enriched sample.

結直腸癌colorectal cancer

本文在一些實施方案中描述的方法包括結直腸癌（也稱為結腸癌）的治療，其包括但不限於晚期結腸癌，惡性結腸癌，轉移性結腸癌，I、II、III或IV期結腸癌,以基因組不穩定性為特徵的結腸癌,以通路改變為特徵的結腸癌,根據結腸癌亞型(CCS)系統分類為CCS1、CCS2或CCS3的結腸癌,根據結直腸癌分配器(CRCA系統)分類為幹細胞樣、杯狀、炎性、過渡放大或腸上皮細胞亞型的結腸癌，根據結腸癌分子亞型(CCMS)系統分類為C1、C2、C3、C4、C5或C6亞型的結腸癌，根據CRC固有亞型(CRCIS)系統分類為A型、B型、或C型亞型的結腸癌，或根據結直腸癌亞型聯盟(CRCSC)分類系統分類為CMS1、CMS2、CMS3或CMS4的結腸癌。在一些實施方案中，結腸癌具有MSI-高或MSI-低的微衛星不穩定性(MSI)狀態。在一些實施方案中，所述個體先前已接受治療(例如，化學療法、放射療法、手術或免疫調節療法)。在一些實施方案中，所述個體對先前的療法(例如，化學療法、放射療法、手術或免疫調節療法)沒有應答。The methods described herein in some embodiments include the treatment of colorectal cancer (also known as colon cancer), which includes but is not limited to advanced colon cancer, malignant colon cancer, metastatic colon cancer, stage I, II, III or IV colon cancer Carcinoma, colon cancer characterized by genomic instability, colon cancer characterized by pathway alterations, colon cancer classified as CCS1, CCS2, or CCS3 according to the Colon Cancer Subtype (CCS) system, according to the Colorectal Cancer Assignment (CRCA) system) of colon cancers classified as stem cell-like, goblet, inflammatory, transitional enlargement, or enterocyte subtypes, classified as C1, C2, C3, C4, C5, or C6 subtypes according to the Colon Cancer Molecular Subtype (CCMS) system Colon cancer classified as subtype A, B, or C according to the CRC Inherent Subtype (CRCIS) system, or CMS1, CMS2, or CMS3 according to the Colorectal Cancer Subtype Consortium (CRCSC) classification system or CMS4 for colon cancer. In some embodiments, the colon cancer has a microsatellite instability (MSI) status of MSI-high or MSI-low. In some embodiments, the individual has previously received treatment (eg, chemotherapy, radiation therapy, surgery, or immunomodulatory therapy). In some embodiments, the individual has not responded to previous therapy (eg, chemotherapy, radiation therapy, surgery, or immunomodulatory therapy).

在各種實施方案中，本文所述的方法用於治療不同階段的結腸癌。在一些實施方案中，所述方法用於治療I期結腸癌。在一些實施方案中，所述方法用於治療II期(例如，IIA、IIB或IIC期)結腸癌。在一些實施方案中，所述方法用於治療III期(例如，IIIA、IIIB或IIIC期)結腸癌。在一些實施方案中，所述方法用於治療IV期(例如IVA期、IVB期或IVC期)結腸癌。在一些實施方案中，所述方法用於治療0期結腸癌(即原位癌)。In various embodiments, the methods described herein are used to treat various stages of colon cancer. In some embodiments, the method is for treating stage I colon cancer. In some embodiments, the method is for treating stage II (eg, stage IIA, IIB, or IIC) colon cancer. In some embodiments, the method is for treating stage III (eg, stage IIIA, IIIB, or IIIC) colon cancer. In some embodiments, the method is used to treat stage IV (eg, stage IVA, stage IVB, or stage IVC) colon cancer. In some embodiments, the method is used to treat stage 0 colon cancer (ie, carcinoma in situ).

在一些實施方案中，結腸癌的特徵在於基因組不穩定性。在一些實施方案中，基因組不穩定性包含基因組DNA的至少一種修飾。在一些實施方案中，所述修飾是染色體不穩定性(CIN)。在一些實施方案中，所述修飾是雜合性丟失(例如染色體DNA的大量丟失)。在一些實施方案中，修改是微衛星不穩定性(MSI)。在一些實施方案中，基因組DNA的修飾包含DNA甲基化修飾或組蛋白修飾。在一些實施方案中，結腸癌的特徵在於總DNA甲基化比正常組織低至少 5%、6%、7%、8%、9%、10%、11%、12%、13%、14%、15%、16%、17%、或18%。在一些實施方案中，基因組DNA的修飾包含CpG島甲基化表型(CIMP)。在一些實施方案中，結腸癌的特徵在於修飾的CpG島甲基化。在一些實施方案中，修飾的CpG島甲基化包含富含CpG的啟動子的高甲基化。In some embodiments, the colon cancer is characterized by genomic instability. In some embodiments, genomic instability comprises at least one modification of genomic DNA. In some embodiments, the modification is chromosomal instability (CIN). In some embodiments, the modification is loss of heterozygosity (eg, massive loss of chromosomal DNA). In some embodiments, the modification is microsatellite instability (MSI). In some embodiments, the modification of genomic DNA comprises DNA methylation modification or histone modification. In some embodiments, colon cancer is characterized by total DNA methylation that is at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14% lower than normal tissue , 15%, 16%, 17%, or 18%. In some embodiments, the modification of the genomic DNA comprises a CpG island methylation phenotype (CIMP). In some embodiments, the colon cancer is characterized by modified CpG island methylation. In some embodiments, the modified CpG island methylation comprises hypermethylation of a CpG-rich promoter.

在不同實施方案中，結腸癌可以在不同的系統下分類為不同的亞型。例如，下述文章中描述了分類系統的一些示例：Rodriguez-Salas et al., Crit Rev Oncol Hematol. 2017 Jan; 109:9-19; De Sousa E Melo et al., Nat Med. 2013 May;19(5):614-8; Sadanandam et al., Nat Med. 2013 May;19(5):619-25; Marisa et al., PloS Med. 2013;10(5); Roepman et al., Int J Cancer. 2014 Feb 1;134(3):552-62; Salazar et al., J Clin Oncol. 2011 Jan 1;29(1):17-24。In different embodiments, colon cancer can be classified under different systems into different subtypes. For example, some examples of classification systems are described in: Rodriguez-Salas et al., Crit Rev Oncol Hematol. 2017 Jan; 109:9-19; De Sousa E Melo et al., Nat Med. 2013 May;19 (5):614-8; Sadanandam et al., Nat Med. 2013 May;19(5):619-25; Marisa et al., PloS Med. 2013;10(5); Roepman et al., Int J Cancer. 2014 Feb 1;134(3):552-62; Salazar et al., J Clin Oncol. 2011 Jan 1;29(1):17-24.

在一些實施方案中，所述結腸癌在結腸癌亞型(CCS)系統下被分類為CCS1。在一些實施方案中，所述結腸癌在結腸癌亞型(CCS)系統下被分類為CCS2。在一些實施方案中，所述結腸癌在結腸癌亞型(CCS)系統下被分類為CCS3。In some embodiments, the colon cancer is classified as CCS1 under the Colon Cancer Subtype (CCS) system. In some embodiments, the colon cancer is classified as CCS2 under the Colon Cancer Subtype (CCS) system. In some embodiments, the colon cancer is classified as CCS3 under the Colon Cancer Subtype (CCS) system.

在一些實施方案中，所述結腸癌在結直腸癌分配器(CRCA系統)下被分類為幹細胞樣亞型。在一些實施方案中，所述結腸癌在結直腸癌分配器(CRCA系統)下被分類為炎性亞型。所述在一些實施方案中，結腸癌在結直腸癌分配器(CRCA系統)下被分類為過渡放大亞型。在一些實施方案中，所述結腸癌在結直腸癌分配器(CRCA系統)下被分類為腸上皮細胞亞型。In some embodiments, the colon cancer is classified as a stem cell-like subtype under the Colorectal Cancer Assignment Algorithm (CRCA system). In some embodiments, the colon cancer is classified as an inflammatory subtype under the Colorectal Cancer Allocation System (CRCA system). In some embodiments, the colon cancer is classified as a transitional amplified subtype under the Colorectal Cancer Algorithm (CRCA system). In some embodiments, the colon cancer is classified as an enterocyte subtype under the Colorectal Cancer Assignment System (CRCA system).

在一些實施方案中，所述結腸癌在結腸癌分子亞型(CCMS)系統下被分類為C1亞型。在一些實施方案中，所述結腸癌在結腸癌分子亞型(CCMS)系統下被分類為C2亞型。在一些實施方案中，所述結腸癌在結腸癌分子亞型(CCMS)系統下被分類為C3亞型。在一些實施方案中，所述結腸癌在結腸癌分子亞型(CCMS)系統下被分類為C4亞型。在一些實施方案中，所述結腸癌在結腸癌分子亞型(CCMS)系統下被分類為C5亞型。在一些實施方案中，所述結腸癌在結腸癌分子亞型(CCMS)系統下被分類為C6亞型。在一些實施方案中，所述結腸癌在結腸癌分子亞型(CCMS)系統下被分類為C1和C5亞型。In some embodiments, the colon cancer is classified as subtype C1 under the Colon Cancer Molecular Subtype (CCMS) system. In some embodiments, the colon cancer is classified as subtype C2 under the Colon Cancer Molecular Subtype (CCMS) system. In some embodiments, the colon cancer is classified as subtype C3 under the Colon Cancer Molecular Subtype (CCMS) system. In some embodiments, the colon cancer is classified as subtype C4 under the Colon Cancer Molecular Subtype (CCMS) system. In some embodiments, the colon cancer is classified as subtype C5 under the Colon Cancer Molecular Subtype (CCMS) system. In some embodiments, the colon cancer is classified as subtype C6 under the Colon Cancer Molecular Subtype (CCMS) system. In some embodiments, the colon cancer is classified as subtypes C1 and C5 under the Colon Cancer Molecular Subtype (CCMS) system.

在一些實施方案中，所述結腸癌在CRC內在亞型(CRCIS)系統下被分類為A型亞型(即MMR缺陷型上皮亞型)。在一些實施方案中，所述結腸癌在CRC內在亞型(CRCIS)系統下被分類為B型亞型(即上皮增殖亞型)。在一些實施方案中，所述結腸癌在CRC內在亞型(CRCIS)系統下被分類為C型亞型。在一些實施方案中，所述結腸癌在結直腸癌亞型聯盟(CRCSC)分類系統下被分類為CMS1。在一些實施方案中，所述結腸癌在結直腸癌亞型聯盟(CRCSC)分類系統下被分類為CMS2。在一些實施方案中，所述結腸癌在結直腸癌亞型聯盟(CRCSC)分類系統下被分類為CMS3。在一些實施方案中，所述結腸癌在結直腸癌亞型聯盟(CRCSC)分類系統下被分類為CMS4。In some embodiments, the colon cancer is classified as a Type A subtype (ie, MMR-deficient epithelial subtype) under the CRC Intrinsic Subtype (CRCIS) system. In some embodiments, the colon cancer is classified as a type B subtype (ie, epithelial proliferation subtype) under the CRC Intrinsic Subtype (CRCIS) system. In some embodiments, the colon cancer is classified as a type C subtype under the CRC Intrinsic Subtype (CRCIS) system. In some embodiments, the colon cancer is classified as CMS1 under the Colorectal Cancer Subtype Consortium (CRCSC) classification system. In some embodiments, the colon cancer is classified as CMS2 under the Colorectal Cancer Subtype Consortium (CRCSC) classification system. In some embodiments, the colon cancer is classified as CMS3 under the Colorectal Cancer Subtype Consortium (CRCSC) classification system. In some embodiments, the colon cancer is classified as CMS4 under the Colorectal Cancer Subtype Consortium (CRCSC) classification system.

治療方法treatment method

在一些實施方案中，本文公開的方法包含投予有效量的DNA損傷劑。本申請所涵蓋的DNA損傷劑包括引起DNA損傷的醫藥上可接受之組合物，包括ssDNA損傷和DSB。在一些實施方案中，DNA損傷劑直接減弱或破壞DNA合成和/或複製。在一些實施方案中，DNA損傷劑降低、阻斷或消除一種或多種DNA DSB修復路徑(包括但不限於HR路徑和NHEJ路徑)和/或ssDNA損傷修復路徑的一種或多種組分的表達和/或活性。所述DNA損傷劑可以是鉑類化合物、DNA交聯劑、拓撲異構酶抑制劑、ATRi或PARPi。在一些實施方案中，鉑基化合物可以是順鉑或卡鉑。在一些實施方案中，拓撲異構酶抑制劑可以是伊立替康或拓撲替康。In some embodiments, the methods disclosed herein comprise administering an effective amount of a DNA damaging agent. DNA damaging agents contemplated herein include pharmaceutically acceptable compositions that cause DNA damage, including ssDNA damage and DSBs. In some embodiments, a DNA damaging agent directly attenuates or disrupts DNA synthesis and/or replication. In some embodiments, the DNA damaging agent reduces, blocks or eliminates the expression and/or expression of one or more components of one or more DNA DSB repair pathways (including but not limited to the HR pathway and the NHEJ pathway) and/or ssDNA damage repair pathways or activity. The DNA damaging agent may be a platinum compound, a DNA cross-linking agent, a topoisomerase inhibitor, ATRi or PARPi. In some embodiments, the platinum-based compound may be cisplatin or carboplatin. In some embodiments, the topoisomerase inhibitor can be irinotecan or topotecan.

在一些實施方案中，本文公開的方法包含投予有效量的PARP抑制劑。本發明涵蓋的PARP抑制劑包括抑制聚(ADP-核醣)聚合酶(PARP)活性的醫藥上可接受之組合物。In some embodiments, the methods disclosed herein comprise administering an effective amount of a PARP inhibitor. PARP inhibitors contemplated by the present invention include pharmaceutically acceptable compositions that inhibit the activity of poly (ADP-ribose) polymerase (PARP).

在一些實施方案中，PARP抑制劑選自：3-胺基苯甲胺、BGD-290、CEP 9722、E7016、伊尼帕利蔔(iniparib)、尼拉帕尼、奧拉帕尼、瑞卡帕尼、他拉唑帕尼和維利帕尼。在一些實施方案中，PARP抑制劑是3-胺基苯甲胺、BGD-290、CEP 9722、E7016、伊尼帕利蔔(iniparib)、尼拉帕尼、奧拉帕尼、瑞卡帕尼、他拉唑帕尼、氟唑帕利或維利帕尼，或其類似物或衍生物。在一些實施方案中，PARP抑制劑是奧拉帕尼。在一些實施方案中，PARP抑制劑是他唑帕尼。在一些實施方案中，PARP抑制劑是瑞卡帕尼。在一些實施方案中，PARP抑制劑是尼拉帕尼。在一些實施方案中，PARP抑制劑選自四環素化合物、4-羥基喹唑啉及其衍生物和羧胺基苯並咪唑及其衍生物。In some embodiments, the PARP inhibitor is selected from the group consisting of: 3-aminobenzylamine, BGD-290, CEP 9722, E7016, iniparib, niraparib, olaparib, rica panib, talazopanib, and veliparib. In some embodiments, the PARP inhibitor is 3-aminobenzylamine, BGD-290, CEP 9722, E7016, iniparib, niraparib, olaparib, ricaparib , talazoparib, fluzoparib, or veliparib, or an analog or derivative thereof. In some embodiments, the PARP inhibitor is olaparib. In some embodiments, the PARP inhibitor is tazopanib. In some embodiments, the PARP inhibitor is ricaparib. In some embodiments, the PARP inhibitor is niraparib. In some embodiments, the PARP inhibitor is selected from tetracycline compounds, 4-hydroxyquinazoline and derivatives thereof, and carboxyaminobenzimidazole and derivatives thereof.

在一些實施方案中，本文公開的方法包含投予有效量的ATRi。本申請涵蓋的ATR抑制劑包括抑制ATR活性的醫藥上可接受之組合物。In some embodiments, the methods disclosed herein comprise administering an effective amount of ATRi. ATR inhibitors contemplated herein include pharmaceutically acceptable compositions that inhibit the activity of ATR.

在一些實施方案中，ATRi選自：五味子乙素、NU6027、達克利司 (NVP-BEZ235)、EPT-46464、都靈2(Torin 2)、VE-821、AZ20、諾華公司的四氫吡唑並[1, 5A]吡嗪鉛、諾華的氮雜苯並咪唑系列鉛、M4344 (VX-803)、BAY1895344、Berzosertib M6620 (VX-970)和Ceralasertib AZD6738。在一些實施方案中，ATRi選自AZD6738、M6620 (VX-970)、BAY1895344和M4344 (VX-803)，它們在過去8年中已進入I期和II期臨床試驗。In some embodiments, ATRi is selected from: Schisandrin, NU6027, Dacres (NVP-BEZ235), EPT-46464, Turin 2 (Torin 2), VE-821, AZ20, tetrahydropyrazole from Novartis Lead [1,5A]pyrazine, Novartis azabenzimidazole series lead, M4344 (VX-803), BAY1895344, Berzosertib M6620 (VX-970) and Ceralasertib AZD6738. In some embodiments, the ATRi is selected from AZD6738, M6620 (VX-970), BAY1895344, and M4344 (VX-803), which have entered Phase I and Phase II clinical trials over the past 8 years.

在一些實施方案中，DNA損傷劑(例如PARP抑制劑或ATRi)的有效量為約1mg至約1000mg，例如約10mg至約800mg，約100mg至約600mg，或約200mg至約500mg。在一些實施方案中，PARP抑制劑或ATR抑制劑的有效量為至少約1mg，例如至少約5 mg、10 mg、15 mg、20 mg、25 mg、50 mg、75 mg、100 mg、150 mg、200 mg、250 mg、300 mg、350 mg、400 mg、450 mg、500 mg、550 mg、600 mg、650 mg、700 mg、750 mg、800 mg、850 mg、900 mg、950 mg、或1000 mg中的一種。In some embodiments, the effective amount of a DNA damaging agent such as a PARP inhibitor or ATRi is from about 1 mg to about 1000 mg, such as from about 10 mg to about 800 mg, from about 100 mg to about 600 mg, or from about 200 mg to about 500 mg. In some embodiments, the effective amount of a PARP inhibitor or ATR inhibitor is at least about 1 mg, such as at least about 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg , 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg, or One of a kind in 1000 mg.

在一些實施方案中，DNA損傷劑(例如PARP抑制劑或ATRi)的有效量不大於約1000mg，例如不大於約950 mg、900 mg、850 mg、800 mg、750 mg、700 mg、650 mg、600 mg、550 mg、500 mg、450 mg、400 mg、350 mg、300 mg、250 mg、200 mg、150 mg、100 mg、75 mg、50 mg、25 mg、20 mg、15 mg、10 mg、5 mg、或1 mg中的任一種。In some embodiments, the effective amount of a DNA damaging agent (such as a PARP inhibitor or ATRi) is no greater than about 1000 mg, such as no greater than about 950 mg, 900 mg, 850 mg, 800 mg, 750 mg, 700 mg, 650 mg, 600 mg, 550 mg, 500 mg, 450 mg, 400 mg, 350 mg, 300 mg, 250 mg, 200 mg, 150 mg, 100 mg, 75 mg, 50 mg, 25 mg, 20 mg, 15 mg, 10 mg , 5 mg, or 1 mg.

在一些實施方案中，DNA損傷劑(例如PARP抑制劑或ATRi)藉由腸道外投予給個體，包括靜脈內、動脈內、腹膜內、肺內、口服、吸入、囊內、肌肉內、氣管內、皮下、眼內、鞘內或經皮。在一些實施方案中，將PARP抑制劑或ATRi經口服給予個體。In some embodiments, the DNA damaging agent (e.g., a PARP inhibitor or ATRi) is administered to a subject by parenteral administration, including intravenous, intraarterial, intraperitoneal, intrapulmonary, oral, inhalation, intrathecal, intramuscular, tracheal Intradermal, subcutaneous, intraocular, intrathecal, or transdermal. In some embodiments, the PARP inhibitor or ATRi is administered orally to an individual.

在一些實施方案中，PARPi與ATRi組合投予。In some embodiments, PARPi is administered in combination with ATRi.

在一些實施方案中，DNA損傷劑(例如PARP抑制劑或ATRi)與另外的抗癌療法或藥劑組合投予。在一些實施方案中，抗癌療法是小分子抑制劑、抗體、細胞療法(即，基於細胞的療法)或核酸。在一些實施方案中，細胞療法是過繼療法、基於T細胞的療法、基於自然殺傷(NK)細胞的療法、嵌合抗原受體(CAR)-T細胞療法、重組T細胞受體(TCR) T細胞療法或基於樹突狀細胞(DC)的療法。在一些實施方案中，所述核酸包括雙鏈RNA (dsRNA)、小幹擾RNA (siRNA)或小髮夾RNA (shRNA)。在一些實施方案中，抗癌療法是化療劑、抗激素劑、抗代謝物化療劑、激酶抑制劑、肽、基因療法、疫苗、基於鉑的化療劑、免疫療法、抗體或檢查點抑制劑。在一些實施方案中，抗癌療法是靶向FGFR的療法。在一些實施方案中，抗癌療法是靶向PTEN的療法。在一些實施方案中，抗癌療法是靶向RB1的療法。在一些實施方案中，抗癌療法是靶向EGFR的療法。在一些實施方案中，抗癌療法是靶向SMARCA4的療法。在一些實施方案中，抗癌療法是靶向TP53的療法。在一些實施方案中，抗癌療法是靶向KRAS的療法。在一些實施方案中，抗癌療法是靶向KRAS(G12C)的療法。在一些實施方案中，抗癌療法是靶向NF2的療法。在一些實施方案中，抗癌療法是靶向VHL的療法。在一些實施方案中，抗癌療法是靶向PBRM1的療法。在一些實施方案中，抗癌療法是免疫療法。In some embodiments, a DNA damaging agent (eg, a PARP inhibitor or ATRi) is administered in combination with another anticancer therapy or agent. In some embodiments, the anticancer therapy is a small molecule inhibitor, antibody, cell therapy (ie, cell-based therapy), or nucleic acid. In some embodiments, the cell therapy is adoptive therapy, T cell based therapy, natural killer (NK) cell based therapy, chimeric antigen receptor (CAR)-T cell therapy, recombinant T cell receptor (TCR) T Cell therapy or dendritic cell (DC) based therapy. In some embodiments, the nucleic acid comprises double-stranded RNA (dsRNA), small interfering RNA (siRNA), or small hairpin RNA (shRNA). In some embodiments, the anticancer therapy is a chemotherapeutic, antihormonal, antimetabolite chemotherapeutic, kinase inhibitor, peptide, gene therapy, vaccine, platinum-based chemotherapeutic, immunotherapy, antibody, or checkpoint inhibitor. In some embodiments, the anticancer therapy is a therapy targeting FGFR. In some embodiments, the anticancer therapy is a PTEN-targeted therapy. In some embodiments, the anticancer therapy is a therapy targeting RB1. In some embodiments, the anticancer therapy is a therapy targeting EGFR. In some embodiments, the anticancer therapy is a therapy targeting SMARCA4. In some embodiments, the anticancer therapy is a therapy targeting TP53. In some embodiments, the anticancer therapy is a KRAS-targeted therapy. In some embodiments, the anticancer therapy is a therapy targeting KRAS(G12C). In some embodiments, the anticancer therapy is a therapy targeting NF2. In some embodiments, the anticancer therapy is a VHL-targeted therapy. In some embodiments, the anticancer therapy is a therapy targeting PBRM1. In some embodiments, the anticancer therapy is immunotherapy.

報告Report

在一些實施方案中，本文提供的方法包括生成報告和/或向當事人提供報告。In some embodiments, the methods provided herein include generating a report and/or providing a report to a party.

在一些實施方案中，根據本申請的報告包括關於藥物敏感性異常的存在或不存在的資訊，例如本文描述的任何藥物敏感性基因中的藥物敏感性突變。在一些實施方案中，根據本申請的報告包括關於耐藥異常的存在或不存在的資訊，例如本文所述的任何耐藥基因中的耐藥突變。In some embodiments, reports according to the present application include information regarding the presence or absence of a drug sensitivity abnormality, such as a drug sensitivity mutation in any of the drug sensitivity genes described herein. In some embodiments, reports according to the present application include information about the presence or absence of drug resistance abnormalities, such as drug resistance mutations in any of the drug resistance genes described herein.

在一個實施方案中，根據本申請的報告表明藥物敏感性異常，例如本文描述的任何藥物敏感性基因中的藥物敏感性突變(和/或耐藥異常，例如本文所述的任何耐藥基因中的耐藥突變)存在於從個體獲得的樣本中。在一個實施方案中，根據本申請的報告表明藥物敏感性異常，例如本文所述的任何藥物敏感性基因中的藥物敏感性突變(和/或耐藥異常，例如本文所述的任何耐藥基因中的耐藥突變)不存在於從個體獲得的樣本中。在一個實施方案中，根據本申請的報告表明藥物敏感性異常，例如本文描述的任何藥物敏感性基因中的藥物敏感性突變(和/或耐藥異常，例如本文所述的任何藥物敏感性基因中的耐藥突變)已在從所述個體獲得的樣本中偵測到。在一個實施方案中，根據本申請的報告表明藥物敏感性異常，例如本文所述的任何藥物敏感性基因中的藥物敏感性突變(和/或耐藥異常，例如本文所述的任何耐藥基因中的耐藥突變)未在從所述個體獲得的樣本中偵測到。在一些實施方案中，所述報告包括從中獲得樣本的個體的識別字。In one embodiment, a report according to the application indicates a drug sensitivity abnormality, such as a drug sensitivity mutation in any of the drug sensitivity genes described herein (and/or a drug resistance abnormality, such as in any of the drug resistance genes described herein resistance mutations) are present in samples obtained from individuals. In one embodiment, a report according to the application indicates a drug sensitivity abnormality, such as a drug sensitivity mutation in any of the drug sensitivity genes described herein (and/or a drug resistance abnormality, such as any of the drug resistance genes described herein The drug resistance mutation in ) was not present in the samples obtained from the individual. In one embodiment, a report according to the application indicates a drug sensitivity abnormality, such as a drug sensitivity mutation in any of the drug sensitivity genes described herein (and/or a drug resistance abnormality, such as any of the drug sensitivity genes described herein The drug resistance mutation in ) has been detected in the sample obtained from said individual. In one embodiment, a report according to the application indicates a drug sensitivity abnormality, such as a drug sensitivity mutation in any of the drug sensitivity genes described herein (and/or a drug resistance abnormality, such as any of the drug resistance genes described herein The drug resistance mutation in ) was not detected in the samples obtained from the individual. In some embodiments, the report includes the identification of the individual from which the sample was obtained.

在一些實施方案中，報告包括關於結直腸癌中藥物敏感性異常(例如，本文所述的任何藥物敏感性基因中的藥物敏感性突變)和/或耐藥異常(例如本文所述的任何耐藥基因中的耐藥突變)的作用的資訊。此類資訊可包括以下一項或多項：關於結直腸癌預後的資訊、關於癌症對DNA損傷劑(例如PARP抑制劑或ATRi)治療的抗性資訊；關於潛在的或建議的治療選擇(例如，使用諸如PARP抑制劑或ATRi或聯合治療等DNA損傷劑的治療)的資訊；或關於應該避免的治療選擇的資訊。在一些實施方案中，該報告包括有關對患有結直腸癌的個體應用治療選擇(例如，包含諸如PARP抑制劑或ATRi的DNA損傷劑的治療)的可能有效性、可接受性和/或可取性的資訊。在一些實施方案中，該報告包括關於投予治療(例如，包含諸如PARP抑制劑或ATRi的DNA損傷劑的治療)的資訊或建議。In some embodiments, the report includes information on drug sensitivity aberrations (e.g., drug sensitivity mutations in any of the drug sensitivity genes described herein) and/or drug resistance aberrations (e.g., any of the drug resistance genes described herein) in colorectal cancer. information on the role of drug resistance mutations in drug genes). Such information may include one or more of the following: information about the prognosis of colorectal cancer, information about the cancer's resistance to treatment with DNA damaging agents (such as PARP inhibitors or ATRi); information about potential or proposed treatment options (such as, Treatment with DNA damaging agents such as PARP inhibitors or ATRi or combination therapy); or information about treatment options that should be avoided. In some embodiments, the report includes information about the likely effectiveness, acceptability, and/or advisability of applying a treatment option (e.g., a treatment comprising a DNA-damaging agent such as a PARP inhibitor or ATRi) to an individual with colorectal cancer sexual information. In some embodiments, the report includes information or recommendations for administering a therapy (eg, a therapy comprising a DNA damaging agent such as a PARP inhibitor or ATRi).

在一些實施方案中，資訊或建議包括治療劑量和/或治療方案(例如，與其他治療組合)。在一些實施方案中，所述報告包括針對至少一種、至少兩種、至少三種、至少四種、至少五種、至少六種、至少七種、至少八種、至少九種、至少十種或更多種治療的資訊或建議。在一些實施方案中，該報告包括不使用至少一種、至少兩種、至少三種、至少四種、至少五種、至少六種、至少七種、至少八種、至少九種、至少十種或更多種治療的資訊或建議。In some embodiments, the information or advice includes therapeutic dosage and/or treatment regimen (eg, in combination with other treatments). In some embodiments, the reporting includes reporting for at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or more Information or advice on various treatments. In some embodiments, the reporting includes not using at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or more Information or advice on various treatments.

本文還提供了根據本申請生成報告的方法。在一些實施方案中，根據本申請的報告藉由包括以下一個或多個步驟的方法生成：從患有結直腸癌的個體獲得樣本，（例如本文所述的樣本）；偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)，或獲知一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)；並生成報告。在一些實施方案中，生成的報告是個性化癌症報告。This article also provides a method for generating reports according to the application. In some embodiments, a report according to the present application is generated by a method comprising one or more of the steps of: obtaining a sample from an individual with colorectal cancer, (such as a sample described herein); detecting one or more One or more drug sensitivity abnormalities (such as drug sensitivity mutations) in drug sensitivity genes and/or one or more drug resistance abnormalities (such as drug resistance mutations) in one or more drug resistance genes, or knowledge of one or more one or more drug sensitivity aberrations (eg, drug sensitivity mutations) in one or more drug sensitivity genes and/or one or more drug resistance aberrations (eg, drug resistance mutations) in one or more drug resistance genes; and generate a report. In some embodiments, the generated report is a personalized cancer report.

根據本申請的報告可以是電子的、基於網路的或紙質的形式。報告可以提供給個體或患者，或者提供給個體或患者以外的(例如患有癌症的個體或患者之外的)個體或實體，例如護理人員、醫生、腫瘤學家、醫院、診所、協力廠商付款人、保險公司或政府實體中的一個或多個。在一些實施方案中，在從個體(例如患有癌症的個體)獲得樣本的約1天或更長、約7天或更長、約14天或更長、約21天或更長、約30天或更長、約45或更長、或約60天或更長中的任一時間內將報告提供或遞送給個體或實體。在一些實施方案中，在獲自個體(例如患有結直腸癌的個體)的樣本中偵測到在一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的約1天或更長、約7天或更長、約14天或更長、約21天或更長、約30天或更長、約45或更長、或約 60天或更長中的任一時間內將報告提供或遞送給個體或實體。在一些實施方案中，在獲自個體(例如患有結直腸癌的個體)的樣本中獲得關於一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或一個或多個耐藥基因中的一種或多種耐藥異常(例如耐藥突變)的資訊約1天或更長、約7天或更長、約14天或更長、約21天或更長、約30天或更長、約45或更長、或約60或更長中的任一時間內將報告提供或遞送給個體或實體。Reports under this application may be in electronic, web-based or paper format. Reports may be provided to the individual or patient, or to individuals or entities other than the individual or patient (eg, outside of the individual or patient with cancer), such as caregivers, physicians, oncologists, hospitals, clinics, third party payments one or more of a person, an insurance company, or a government entity. In some embodiments, about 1 day or more, about 7 days or more, about 14 days or more, about 21 days or more, about 30 days or more of obtaining the sample from the individual (eg, an individual with cancer) The report is provided or delivered to the individual or entity for any of any of 45 days or longer, about 45 days or longer, or about 60 days or longer. In some embodiments, one or more drug sensitivity aberrations (eg, drug sensitivity mutations) in one or more drug sensitivity genes are detected in a sample obtained from an individual (eg, an individual with colorectal cancer) ) and/or about 1 day or more, about 7 days or more, about 14 days or more, about 21 days of one or more drug resistance abnormalities (e.g., drug resistance mutations) in one or more drug resistance genes or longer, about 30 days or longer, about 45 days or longer, or about 60 days or longer, the report is provided or delivered to the individual or entity. In some embodiments, information about one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) in one or more drug sensitivity genes is obtained in a sample obtained from an individual (eg, an individual with colorectal cancer) and and/or information on one or more resistance abnormalities (e.g., resistance mutations) in one or more resistance genes of about 1 day or longer, about 7 days or longer, about 14 days or longer, about 21 days or The report is provided or delivered to the individual or entity for any of longer, about 30 days or longer, about 45 or longer, or about 60 or longer.

偵測突變等異常Detect abnormalities such as mutations

在一些實施方案中，藥物敏感性突變或耐藥突變選自剪接位點突變、無義突變、移碼突變和錯義突變。在一些實施方案中，藥物敏感性突變或耐藥突變是有害的或致病的(即失活的)突變。某些基因的致病性失活突變(功能喪失)可以藉由閱讀已發表的科學文獻中的實驗證據和檢查可能被破壞的關鍵區域來確定，包括但不限於移碼、錯義突變、截短突變、缺失、拷貝數變異、無義突變以及基因的丟失或缺失。致病或失活突變包括但不限於純合缺失、雙等位基因(雙命中)突變、剪接位點突變(例如，第二個或額外的剪接位點突變)、移碼突變和編碼區的無義突變、具有確認影響的錯義突變。In some embodiments, the drug sensitivity mutation or drug resistance mutation is selected from splice site mutations, nonsense mutations, frameshift mutations, and missense mutations. In some embodiments, the drug sensitivity mutation or drug resistance mutation is a deleterious or pathogenic (ie, inactivating) mutation. Pathogenic inactivating mutations (loss of function) of certain genes can be identified by reading experimental evidence in the published scientific literature and examining critical regions that may be disrupted, including but not limited to frameshifts, missense mutations, truncating Short mutations, deletions, copy number variations, nonsense mutations, and loss or deletion of genes. Pathogenic or inactivating mutations include, but are not limited to, homozygous deletions, biallelic (double hit) mutations, splice site mutations (eg, second or additional splice site mutations), frameshift mutations, and mutations in coding regions. Nonsense mutations, missense mutations with confirmed effects.

藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)可以使用業內已知的任意合適方法來偵測，例如核酸雜交測定、免疫螢光染色、免疫印跡、基於擴增的分析(例如PCR)、PCR-RFLP分析、即時PCR、定序(例如Sanger定序或下一代定序)、篩選分析(例如，使用染色體組型方法)、例如DNA定序、RNA-seq、ChIP-seq、DNase-seq、微球菌核酸酶 (MNase)-seq(例如用於偵測基因調控區的核小體排列)、螢光原位雜交 (FISH)、單離螢光原位雜交(Break away FISH)、光譜核型分析、多重FISH、比較基因組雜交、原位雜交、單特異性引子PCR (SSP-PCR)、高效液相層析 (HPLC)或質譜基因分型。在美國專利號9340830和WO2012092426A1中描述了分析樣本的方法，例如偵測核酸分子，這些專利在此藉由引用整體併入本文。Drug susceptibility abnormalities (e.g., drug sensitivity mutations) and/or drug resistance abnormalities (e.g., drug resistance mutations) can be detected using any suitable method known in the art, such as nucleic acid hybridization assays, immunofluorescence staining, western blotting, based on Amplified analysis (e.g. PCR), PCR-RFLP analysis, real-time PCR, sequencing (e.g. Sanger sequencing or next generation sequencing), screening analysis (e.g. using karyotyping methods), e.g. DNA sequencing, RNA- seq, ChIP-seq, DNase-seq, micrococcal nuclease (MNase)-seq (e.g. for detection of nucleosome alignment in gene regulatory regions), fluorescence in situ hybridization (FISH), isolated fluorescence in situ Hybridization (Break away FISH), spectral karyotyping, multiplex FISH, comparative genomic hybridization, in situ hybridization, single specific primer PCR (SSP-PCR), high performance liquid chromatography (HPLC) or mass spectrometry genotyping. Methods of analyzing samples, such as detecting nucleic acid molecules, are described in US Pat. No. 9340830 and WO2012092426A1, which are hereby incorporated by reference in their entirety.

原位雜交方法in situ hybridization method

在一些實施方案中，使用原位雜交法例如螢光原位雜交(FISH)法偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。In some embodiments, one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) and/or drug resistance abnormalities (e.g., drug resistance mutation).

在一些實施方案中，FISH分析用於鑒定導致如本文所述突變的染色體重排。在一些實施方案中，FISH分析用於鑒定包含本文所述的一種或多種藥物敏感性突變或/或耐藥突變的RNA分子或蛋白質。在一些實施方案中，FISH分析用於鑒定RNA或蛋白質的異常表達。在一些實施方案中，FISH分析用於鑒定DNA、RNA或蛋白質的異常修飾。進行FISH的方法是業內已知的並且可以用於幾乎任何類型的組織。在一些實施方案中，蛋白質探針被標記(例如螢光或放射性標記)並與含有靶蛋白質或受體的組織一起溫育，並且可以藉由偵測標記的蛋白質探針來定位(例如藉由顯微鏡)交互作用位點。在FISH分析中，可偵測標記的例如螢光標記的核酸探針可以與DNA(例如染色體)或 RNA(例如mRNA)的特定區域結合，然後藉由例如顯微鏡進行檢查。DNA或RNA分子首先固定在載玻片上，然後標記的探針與DNA或RNA分子雜交，然後實現視覺化，例如，使用業內已知的基於酶聯標記的偵測方法。通常，FISH分析的解析度約為60到100000個核苷酸的偵量測，例如60鹼基對(bp)到100千鹼基對的DNA。FISH分析中使用的核酸探針包括單鏈核酸。這種探針的長度通常至少約為50個核苷酸。在一些實施方案中，探針包含約100至約500個核苷酸。與著絲粒DNA和基因座特異性DNA或RNA雜交的探針可商購，例如購自Vysis公司(Downers Grove, 伊利諾州)、Molecular Probes公司(Eugene,俄勒岡)或Cytocell (Oxfordshire，英國)。或者，探針可以藉由準則技術從染色體或基因組DNA或其他核酸(或多肽)來源非商業化地製備。探針、標記和雜交方法的例子是業內已知的。In some embodiments, FISH analysis is used to identify chromosomal rearrangements that result in mutations as described herein. In some embodiments, FISH analysis is used to identify RNA molecules or proteins comprising one or more drug-sensitivity mutations or/or drug-resistance mutations described herein. In some embodiments, FISH analysis is used to identify aberrant expression of RNA or protein. In some embodiments, FISH analysis is used to identify abnormal modifications of DNA, RNA or proteins. Methods of performing FISH are known in the art and can be used on virtually any type of tissue. In some embodiments, protein probes are labeled (e.g., fluorescently or radiolabeled) and incubated with tissue containing the target protein or receptor, and can be localized by detecting the labeled protein probe (e.g., by microscope) interaction sites. In FISH analysis, detectably labeled, eg, fluorescently labeled, nucleic acid probes can be bound to specific regions of DNA (eg, chromosome) or RNA (eg, mRNA) and then examined, eg, by microscopy. DNA or RNA molecules are first immobilized on glass slides, then labeled probes are hybridized to the DNA or RNA molecules, and then visualized, for example, using enzyme-linked label-based detection methods known in the art. Typically, the resolution of FISH analysis is about 60 to 100,000 nucleotides of detection, eg, 60 base pairs (bp) to 100 kilobase pairs of DNA. Nucleic acid probes used in FISH analysis include single-stranded nucleic acids. Such probes are generally at least about 50 nucleotides in length. In some embodiments, a probe comprises about 100 to about 500 nucleotides. Probes that hybridize to centromere DNA and locus-specific DNA or RNA are commercially available, e.g. from Vysis (Downers Grove, IL), Molecular Probes (Eugene, OR) or Cytocell (Oxfordshire, UK) . Alternatively, probes can be prepared non-commercially by standard techniques from chromosomal or genomic DNA or other nucleic acid (or polypeptide) sources. Examples of probes, labels and hybridization methods are known in the art.

FISH方法的幾種變體在業內中是已知的並且適合根據本申請的方法使用，包括單分子RNA FISH、Fiber FISH、Q-FISH、Flow-FISH、MA-FISH、break- away FISH、雜交融合-FISH和multi-fluor FISH或mFISH。在一些實施方案中，可以藉由免疫螢光染色偵測蛋白質，例如，使用抗體或其抗原結合片段。Several variants of FISH methods are known in the art and are suitable for use according to the methods of the present application, including single molecule RNA FISH, Fiber FISH, Q-FISH, Flow-FISH, MA-FISH, break-away FISH, hybridization Fusion-FISH and multi-fluor FISH or mFISH. In some embodiments, proteins can be detected by immunofluorescent staining, eg, using antibodies or antigen-binding fragments thereof.

基於陣列的方法Array-based approach

在一些實施方案中，使用基於陣列的方法，例如基於陣列的比較基因組雜交(CGH)方法，偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。在基於陣列的CGH方法中，第一個核酸樣本(例如，來自樣本，例如來自腫瘤)用第一個標記物標記，而第二個核酸樣本(例如，對照，例如來自健康細胞/組織)用第二個標記物標記。在一些實施方案中，將等量的兩種樣本混合並共同雜交到由數千個均勻間隔的克隆DNA片段或寡核苷酸組成的DNA微陣列中，這些克隆DNA片段或寡核苷酸已被一式三份地點在陣列上。雜交後，利用數位成像系統捕獲和量化每個雜交螢光基團的相對螢光強度。所得螢光強度的比率與兩個樣本中DNA序列的拷貝數比率成正比。在一些實施方案中，在存在染色體缺失或增殖的情況下，偵測來自兩個標記的信號比率的差異，並且該比率提供了對拷貝數的量測值。基於陣列的CGH也可以使用單色標記來執行。在單色CGH中，對照(例如，對照核酸樣本，例如來自健康細胞/組織)被標記並與一個陣列雜交並讀取絕對信號，並且測試樣本(例如源自個體或腫瘤的核酸樣本)被標記並與第二個陣列(具有相同內容)雜交並讀取絕對信號。拷貝數差異是根據來自兩個陣列的絕對信號計算的。在一些實施方案中，該陣列用於偵測樣本中的RNA。在一些實施方案中，所得螢光強度比與兩個樣本中RNA量的比成比例，例如反映異常表達水準。在一些實施方案中，所述陣列是蛋白質陣列或蛋白質晶片。In some embodiments, one or more drug sensitivity abnormalities (e.g., drug sensitivity mutations) and/or drug resistance abnormalities ( such as resistance mutations). In array-based CGH methods, a first nucleic acid sample (e.g., from a sample, e.g., from a tumor) is labeled with a first marker, while a second nucleic acid sample (e.g., a control, e.g., from healthy cells/tissue) is labeled with The second marker flag. In some embodiments, equal amounts of the two samples are mixed and co-hybridized into a DNA microarray consisting of thousands of evenly spaced clonal DNA fragments or oligonucleotides that have been were located on the array in triplicate. After hybridization, the relative fluorescence intensity of each hybridized fluorophore is captured and quantified using a digital imaging system. The ratio of the resulting fluorescence intensities is directly proportional to the ratio of the copy numbers of the DNA sequences in the two samples. In some embodiments, a difference in the ratio of signals from the two markers is detected in the presence of chromosomal deletion or multiplication, and the ratio provides a measure of copy number. Array-based CGH can also be performed using single-color labeling. In single-color CGH, controls (e.g., control nucleic acid samples, e.g., from healthy cells/tissue) are labeled and hybridized to one array and absolute signals are read, and test samples (e.g., nucleic acid samples from individuals or tumors) are labeled And hybridize to a second array (with the same content) and read the absolute signal. Copy number differences were calculated from the absolute signal from the two arrays. In some embodiments, the array is used to detect RNA in a sample. In some embodiments, the resulting ratio of fluorescence intensities is proportional to the ratio of RNA amounts in the two samples, eg, reflecting abnormal expression levels. In some embodiments, the array is a protein array or protein wafer.

基於擴增的方法Amplification-based methods

在一些實施方案中，使用基於擴增的方法偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。如業內已知的，在這種基於擴增的方法中，核酸樣本，例如源自個體或腫瘤的樣本，被用作使用一種或多種寡核苷酸或引子(例如本文提供的一種或多種寡核苷酸或引子)的擴增反應(例如PCR)中的範本。可以基於擴增產物的存在或不存在來確定本申請樣本中一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的存在。定量擴增方法也是業內已知的並且可以根據本文提供的方法使用。已知的基因核苷酸序列足以使熟習此項技術者能夠習知選擇引子以擴增基因的任何部分。也可以使用螢光定量PCR。在螢光定量 PCR中，基於螢光信號的量進行定量，例如TaqMan和Sybr green。In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) and/or drug resistance abnormalities (eg, drug resistance mutations) of the present application are detected using amplification-based methods. As is known in the art, in such amplification-based methods, a nucleic acid sample, such as that derived from an individual or a tumor, is used as a primer using one or more oligonucleotides or primers (such as one or more of the oligonucleotides provided herein). nucleotides or primers) in amplification reactions such as PCR. The presence or absence of one or more drug sensitivity abnormalities (eg drug sensitivity mutations) and/or drug resistance abnormalities (eg drug resistance mutations) in the sample of the present application can be determined based on the presence or absence of amplification products. Quantitative amplification methods are also known in the art and can be used according to the methods provided herein. The known nucleotide sequence of a gene is sufficient to enable one skilled in the art to select primers to amplify any portion of the gene. Fluorescent quantitative PCR can also be used. In fluorescent quantitative PCR, quantification is based on the amount of fluorescent signal, such as TaqMan and Sybr green.

適合根據本文提供的方法使用的其他擴增方法包括，例如，連接酶鏈式反應(LCR)、轉錄擴增、自主序列複製、點PCR和連接連接子PCR(linker adapter PCR)。Other amplification methods suitable for use in accordance with the methods provided herein include, for example, ligase chain reaction (LCR), transcriptional amplification, autonomous sequence replication, spot PCR, and linker adapter PCR.

定序Sequencing

在一些實施方案中，使用定序方法偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。業內已知的任何定序方法都可以用於偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。可以使用的示例性定序方法包括那些基於Maxam和Gilbert或Sanger開發的技術的方法。在一些實施方案中，定序方法是DNA定序。在一些實施方案中，定序方法是RNA定序。也可以使用自動定序程式，例如，包括質譜定序。在一些實施方案中，對整個基因或基因產物(例如RNA、多肽)進行定序。在一些實施方案中，對基因或基因產物(例如RNA、多肽)的相關部分進行定序，例如已知含有突變或修飾的核酸或多肽片段。在一些實施方案中，異常包括異常表達。在一些實施方案中，異常包括異常修飾(例如，在DNA、RNA或多肽水準上)。In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) and/or drug resistance abnormalities (eg, drug resistance mutations) of the present application are detected using sequencing methods. Any sequencing method known in the art can be used to detect one or more drug sensitivity abnormalities (eg drug sensitivity mutations) and/or drug resistance abnormalities (eg drug resistance mutations) of the present application. Exemplary sequencing methods that can be used include those based on techniques developed by Maxam and Gilbert or Sanger. In some embodiments, the sequencing method is DNA sequencing. In some embodiments, the sequencing method is RNA sequencing. Automated sequencing programs can also be used, including, for example, mass spectrometric sequencing. In some embodiments, an entire gene or gene product (eg, RNA, polypeptide) is sequenced. In some embodiments, relevant portions of a gene or gene product (eg, RNA, polypeptide) are sequenced, eg, nucleic acid or polypeptide fragments known to contain mutations or modifications. In some embodiments, abnormalities include aberrant expression. In some embodiments, an abnormality includes an abnormal modification (eg, at the DNA, RNA, or polypeptide level).

在一些實施方案中，使用基於雜交捕獲的定序(基於雜交捕獲的下一代定序 (NGS))，例如，使用基於連接子連接的文庫偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。參見，例如，Frampton, G.M. et al. (2013) Nat. Biotech. 31:1023-1031。在一些實施方案中，使用下一代定序(NGS)偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。下一代定序包括以高度平行的方式(例如，可以同時對超過105個分子進行定序)確定個體核酸分子或個體核酸分子的克隆擴增替代品的核苷酸序列的任何定序方法。適用於根據本文提供的方法使用的下一代定序方法是業內已知的並且包括但不限於大規模平行短讀長定序、基於範本的定序、焦磷酸定序、包括對DNA合成過程中染料標記核苷酸的連續摻入進行成像的即時定序、奈米孔定序、雜交定序、基於奈米電晶體陣列的定序、聚合酶克隆定序(polony sequencing)、基於掃描隧道顯微鏡 (STM)的定序、或基於奈米線分子感測器的定序。參見，例如，Metzker, M. (2010) Nature Biotechnology Reviews 11:31-46，其藉由引用併入本文。可用於偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的示例性NGS方法和平臺包括但不限於來自Helicos BioSciences (Cambridge, MA, USA)的HeliScope基因定序系統、來自Pacific Biosciences (Menlo Park, CA, USA)的PacBio RS系統、大規模並行短讀定序例如Solexa定序儀和來自Illumina Inc.(San Diego, CA, USA)的其他方法和平臺、來自454 LifeSciences (Branford, CT, USA)的454定序、來自ThermoFisher (Waltham, MA, USA)的半導體定序(Ion Torrent定序)、或來自Applied Biosystems (Foster City, CA, USA) 的SOLiD定序儀。可用於偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的其他示例性方法和平臺包括但不限於來自Roche(Basel, CHE)的基因組定序儀(GS )的FLX系統、G.007 polonator系統、Solexa基因組分析儀、來自Illumina Inc.(San Diego, CA, USA)的 HiSeq 2500、HiSeq3000、HiSeq 4000和NovaSeq 6000 平臺。In some embodiments, hybridization-capture-based sequencing (hybridization-capture-based next-generation sequencing (NGS)), e.g., using a linker ligation-based library, is used to detect one or more drug susceptibility abnormalities of the present application (e.g., drug susceptibility mutations) and/or resistance abnormalities (e.g. drug resistance mutations). See, eg, Frampton, G.M. et al. (2013) Nat. Biotech. 31:1023-1031. In some embodiments, one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) and/or drug resistance abnormalities (eg, drug resistance mutations) of the present application are detected using next generation sequencing (NGS). Next generation sequencing includes any sequencing method that determines the nucleotide sequence of an individual nucleic acid molecule or a clonally amplified surrogate of an individual nucleic acid molecule in a highly parallel fashion (eg, more than 105 molecules can be sequenced simultaneously). Next-generation sequencing methods suitable for use in accordance with the methods provided herein are known in the art and include, but are not limited to, massively parallel short-read sequencing, template-based sequencing, pyrosequencing, including sequencing of DNA during synthesis. Immediate sequencing for imaging by sequential incorporation of dye-labeled nucleotides, nanopore sequencing, hybridization sequencing, nanotransistor array-based sequencing, polony sequencing, scanning tunneling microscopy-based (STM) sequencing, or nanowire-based molecular sensor sequencing. See, eg, Metzker, M. (2010) Nature Biotechnology Reviews 11:31-46, which is incorporated herein by reference. Exemplary NGS methods and platforms that can be used to detect one or more drug sensitivity aberrations (e.g., drug sensitivity mutations) and/or drug resistance aberrations (e.g., drug resistance mutations) of the present application include, but are not limited to, those from Helicos BioSciences (Cambridge, MA, USA) HeliScope gene sequencing system, PacBio RS system from Pacific Biosciences (Menlo Park, CA, USA), massively parallel short-read sequencing such as Solexa sequencer and from Illumina Inc. (San Diego, CA, USA), 454 sequencing from 454 LifeSciences (Branford, CT, USA), semiconductor sequencing (Ion Torrent sequencing) from ThermoFisher (Waltham, MA, USA), or from Applied Biosystems (Foster City , CA, USA) SOLiD sequencer. Other exemplary methods and platforms that can be used to detect one or more drug sensitivity aberrations (e.g. drug sensitivity mutations) and/or drug resistance aberrations (e.g. drug resistance mutations) of the present application include but are not limited to methods and platforms from Roche (Basel, CHE ) Genome Sequencer (GS ) FLX system, G.007 polonator system, Solexa Genome Analyzer, HiSeq 2500, HiSeq3000, HiSeq 4000 and NovaSeq 6000 platforms from Illumina Inc. (San Diego, CA, USA).

在本文提供的任何方法的一些實施方案中，所述方法包含提供來自患有結直腸癌的個體的樣本，其中所述樣本包含一種或多種多肽。在一些實施方案中，所述方法進一步包含從樣本中的一種或多種多肽製備蛋白質或多肽文庫(例如用於質譜)。用於蛋白質定序或質譜分析的樣本或文庫製備方法是眾所周知的。例如，參見Laura Restrepo-Pérez et al (2018) Nat Nanotechnol, 13: 786–796)。In some embodiments of any of the methods provided herein, the method comprises providing a sample from an individual with colorectal cancer, wherein the sample comprises one or more polypeptides. In some embodiments, the method further comprises preparing a protein or polypeptide library from the one or more polypeptides in the sample (eg, for mass spectrometry). Sample or library preparation methods for protein sequencing or mass spectrometry are well known. See, for example, Laura Restrepo-Pérez et al (2018) Nat Nanotechnol, 13: 786–796).

在本文提供的任何方法的一些實施方案中，所述方法包含提供來自患有結直腸癌的個體的樣本，其中所述樣本包含一種或多種核酸。在一些實施方案中，所述方法進一步包含從樣本中的一種或多種核酸製備核酸定序文庫。用於製備核酸定序文庫的方法，例如，適用於本文所述的任何定序方法(例如下一代定序)，是業內已知的。在一些實施方案中，定序文庫藉由如Frampton et al (2013) Nat Biotechnol, 31:1023-1031中所述製備。在一些實施方案中，所述文庫被擴增。用於擴增核酸文庫的方法(例如包括添加樣本索引和/或條碼的步驟)是業內已知的。在一些實施方案中，使用PCR擴增定序文庫。在一些實施方案中，定序文庫藉由如Frampton et al (2013) Nat Biotechnol, 31:1023-1031中所述進行擴增。在一些實施方案中，所述方法進一步包含選擇性地增濃一種或多種核酸(例如包含本文所述的一種或多種基因改變的一種或多種核酸)以產生增濃的樣本。在一些實施方案中，所述選擇性增濃包含將誘餌(例如本文所述的誘餌)與樣本(例如文庫)組合，從而使誘餌與樣本(例如文庫中)中的一種或多種核酸雜交，並產生核酸雜交體；單離核酸雜交體以產生增濃樣本。在一些實施方案中，如Frampton et al (2013) Nat Biotechnol, 31:1023-1031中所述進行選擇性增濃。在一些實施方案中，所述方法進一步包含擴增(例如使用PCR)增濃樣本中的核酸。在一些實施方案中，所述方法還包含對增濃的樣本進行定序，從而產生多個定序讀數。在一些實施方案中，使用業內已知或本文提供的任何定序方法進行定序。在一些實施方案中，使用Illumina定序儀進行定序。在一些實施方案中，如Frampton et al (2013) Nat Biotechnol, 31:1023-1031中所述進行定序。在一些實施方案中，所述方法進一步包含分析多個定序讀數，例如，分析本文所述的一種或多種基因改變的存在。在一些實施方案中，分析步驟包括將多個定序讀數與人類基因組比對（例如人類基因組版本hg19，例如使用任意合適的方法，例如BWA比對器）。在一些實施方案中，分析步驟進一步包含去除PCR重複讀數，和/或收集序列指標(例如，使用Picard 1.47和/或Samtools)。在一些實施方案中，分析步驟包含（例如使用GATK）執行局部比對優化。在一些實施方案中，分析步驟進一步包括變體識別(variant calling)。在一些實施方案中，分析步驟包含偵測鹼基取代，例如，使用貝葉斯方法。在一些實施方案中，分析步驟包含偵測插入缺失，例如使用Bruijn方法。在一些實施方案中，分析步驟包含偵測拷貝數改變，例如使用比較基因組雜交樣方法。在一些實施方案中，分析步驟包含偵測基因組重排和/或基因融合，例如藉由分析嵌合讀數對。在一些實施方案中，如Frampton et al (2013) Nat Biotechnol, 31:1023-1031中所述進行分析步驟。在一些實施方案中，所述方法進一步包含基於分析步驟偵測本文所述的一種或多種基因改變。In some embodiments of any of the methods provided herein, the method comprises providing a sample from an individual with colorectal cancer, wherein the sample comprises one or more nucleic acids. In some embodiments, the method further comprises preparing a nucleic acid sequencing library from the one or more nucleic acids in the sample. Methods for preparing nucleic acid sequencing libraries, eg, applicable to any of the sequencing methods described herein (eg, next generation sequencing), are known in the art. In some embodiments, the sequencing library is prepared as described in Frampton et al (2013) Nat Biotechnol, 31:1023-1031. In some embodiments, the library is amplified. Methods for amplifying nucleic acid libraries (eg, including steps of adding sample indexes and/or barcoding) are known in the art. In some embodiments, PCR is used to amplify the sequenced library. In some embodiments, the sequenced library is amplified by amplification as described in Frampton et al (2013) Nat Biotechnol, 31:1023-1031. In some embodiments, the method further comprises selectively enriching one or more nucleic acids (eg, one or more nucleic acids comprising one or more genetic alterations described herein) to produce an enriched sample. In some embodiments, the selective enrichment comprises combining a bait (e.g., a bait described herein) with a sample (e.g., a library) such that the bait hybridizes to one or more nucleic acids in the sample (e.g., in the library), and Generate nucleic acid hybrids; isolate nucleic acid hybrids to generate enriched samples. In some embodiments, selective enrichment is performed as described in Frampton et al (2013) Nat Biotechnol, 31:1023-1031. In some embodiments, the method further comprises amplifying (eg, using PCR) the nucleic acid in the enriched sample. In some embodiments, the method further comprises sequencing the enriched sample, thereby generating a plurality of sequencing reads. In some embodiments, sequencing is performed using any sequencing method known in the art or provided herein. In some embodiments, sequencing is performed using an Illumina sequencer. In some embodiments, sequencing is performed as described in Frampton et al (2013) Nat Biotechnol, 31:1023-1031. In some embodiments, the method further comprises analyzing a plurality of sequenced reads, eg, analyzing for the presence of one or more genetic alterations described herein. In some embodiments, the step of analyzing includes aligning the plurality of sequenced reads to a human genome (eg, human genome version hg19, eg, using any suitable method, eg, BWA aligner). In some embodiments, the analyzing step further comprises removing PCR duplicate reads, and/or collecting sequence indices (eg, using Picard 1.47 and/or Samtools). In some embodiments, the analyzing step comprises performing local alignment optimization (eg, using GATK). In some embodiments, the analyzing step further comprises variant calling. In some embodiments, the analyzing step comprises detecting base substitutions, eg, using Bayesian methods. In some embodiments, the analyzing step comprises detecting indels, for example using the Bruijn method. In some embodiments, the analyzing step comprises detecting copy number alterations, for example using comparative genomic hybridization methods. In some embodiments, the analyzing step comprises detecting genomic rearrangements and/or gene fusions, eg, by analyzing chimeric read pairs. In some embodiments, the analyzing step is performed as described in Frampton et al (2013) Nat Biotechnol, 31:1023-1031. In some embodiments, the method further comprises detecting one or more genetic alterations described herein based on the analyzing step.

誘餌、捕獲多肽、捕獲核酸、探針、引子和寡核苷酸Baits, capture polypeptides, capture nucleic acids, probes, primers and oligonucleotides

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與多個藥物敏感性基因和/或多個耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為結合多種藥物敏感性基因和/或多種耐藥基因的表達產物(例如多肽)(或其部分)。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與多個藥物敏感性基因、和/或多個耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，被配置為與多種藥物敏感性基因和/或多種耐藥基因的表達產物(例如多肽)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with a plurality of drug susceptibility genes and/or Or multiple drug resistance genes, or RNAs encoded by them hybridize. In some embodiments, multiple capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to bind multiple drug susceptibility genes and/or multiple An expression product (such as a polypeptide) (or part thereof) of a drug-resistant gene. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with A plurality of drug sensitivity genes, and/or a plurality of drug resistance genes, or RNAs encoded by them are hybridized. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to interact with a plurality of drug Sensitive genes and/or expression products (such as polypeptides) of various drug-resistant genes are combined.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表1或2提供的任意至少1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表1或2提供的任意至少1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了包含多個捕獲核酸分子(或探針，引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表1或2提供的任意至少1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為結合表1或2提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any of the molecules provided in Table 1 or 2 is provided. 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug susceptibility genes or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match any of at least 1 of the molecules provided in Table 1 or 2 is provided. , 5, 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by the drug susceptibility genes are combined. In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) configured to match any of the capture nucleic acid molecules provided in Table 1 or 2 is provided. At least 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug susceptibility genes or RNAs encoding them are hybridized. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured as a binding surface Combination of at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by drug sensitivity genes provided by 1 or 2.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3中提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3中提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因，或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，所述套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為結合表3提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any 1, Hybridization of 5, 10, 20, 30, 40, 50, 100, 200 or all drug susceptibility genes, or RNAs encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to associate with at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides encoded by the drug susceptibility genes (or portions thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with At least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the drug susceptibility genes provided in Table 3, or RNA hybrids encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to bind Combination of polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug sensitivity genes provided in Table 3.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3a)提供的任意至少1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3a)提供的任意至少1、5、10、20、30個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3a)中提供的至少任意1、5、10、20、30個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3a)提供的至少任意1、5、10、20、30個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match any of at least 1 of the molecules provided in Table 3a) is provided. , 5, 10, 20, 30, 40 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits, each comprising a capture polypeptide molecule) configured to match any of at least 1, 5, 10, 20, 30 or all of the polypeptides encoded by the drug susceptibility genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with At least any 1, 5, 10, 20, 30 or all of the drug sensitivity genes provided in Table 3a), or RNA hybrids encoding them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 3a) Combination of polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3b)提供的至少任意1、5、10、20個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3b)提供的至少任意1、5、10、20個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3b)提供的至少任意1、5、10、20個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3b)提供的任意至少1、5、10、20個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 3b) is provided. , 5, 10, 20 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, , and 5, 10, 20 or all polypeptides (or parts thereof) encoded by drug susceptibility genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 3b) at least any 1, 5, 10, 20 or all of the drug sensitivity genes provided, or RNA hybrids encoded by them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 3b) Combination of any at least 1, 5, 10, 20 or all of the polypeptides encoded by the drug sensitivity genes (or parts thereof) provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3c)中提供的至少任意1、5、10、20、30個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3c)提供的至少任意1、5、10、20、30個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3c)提供的至少任意1、5、10、20、30個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3c)提供的至少任意1、5、10、20、30個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any of the molecules provided in Table 3c) is provided. Hybridization of 1, 5, 10, 20, 30 or all drug susceptibility genes, or RNAs encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, 5, 10, 20, 30 or all of the polypeptides encoded by the drug susceptibility genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 3c) at least any 1, 5, 10, 20, 30 or all of the drug sensitivity genes provided, or RNA hybrids encoded by them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 3c) Combining polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3d)提供的任意至少1、5、10、20、30個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3d)提供的至少任意1、5、10、20、30個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3d)提供的任意至少1、5、10、20、30個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為結合由表3d)提供的至少任意1、5、10、20、30個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match any of the at least 1 molecules provided in Table 3 d) is provided. , 5, 10, 20, 30 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, 5, 10, 20, 30 or all of the polypeptides encoded by the drug susceptibility genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Any of at least 1, 5, 10, 20, 30 or all of the drug sensitivity genes provided in Table 3d), or RNA hybrids encoding them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to bind Combination of at least any 1, 5, 10, 20, 30 or all of the polypeptides (or parts thereof) encoded by the drug sensitivity genes provided in Table 3d).

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3e)中提供的至少任意1、5、10、20、30、40、50、60、70、80、90個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3e)提供的至少任意1、5、10、20、30、40、50、60、70、80、90個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表3e)提供的至少任意1、5、10、20、30、40、50、60、70、80、90個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表3e)提供的至少任意1、5、10、20、30、40、50、60、70、80、90個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any of the provided in Table 3e) is provided. Hybridization of 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or all drug susceptibility genes, or RNAs encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, , and 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or all of the polypeptides encoded by the drug susceptibility genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 3e) at least any 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or all of the drug sensitivity genes provided in Table 3e), or their encoded RNA hybrids. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 3e) Combining polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or all of the provided drug sensitivity genes.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表A中提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被被配置為與表A提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表A提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表A提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table A is provided. , 5, 10, 20, 30, 40 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides (or parts thereof) encoded by the drug susceptibility genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with At least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided in Table A, or their encoded RNA hybrids. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table A combination of at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug sensitivity genes (or parts thereof) provided by A.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any 1 , Hybridization of 5, 10, 20, 30, 40, 50, 100, 200 or all drug susceptibility genes, or RNAs encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, 5 provided in Table 4 is provided. , 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by the drug susceptibility genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with At least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the drug sensitivity genes provided in Table 4, or their encoded RNA hybrids. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 4 Combination of polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4a)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被被配置為與表4a)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4a)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4a)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 4a) is provided. , 5, 10, 20, 30, 40 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any one of the molecules provided in Table 4a) is provided. , 5, 10, 20, 30, 40 or all of the polypeptides (or parts thereof) encoded by the drug susceptibility genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with At least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided in Table 4a), or RNA hybrids encoding them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 4a) Combination of polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4b)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4b)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4b)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4b)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 4b) is provided. , 5, 10, 20, 30, 40 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides (or parts thereof) encoded by the drug susceptibility genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 4b) at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided, or RNA hybrids encoding them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 4b) Combination of polypeptides encoded by at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4c)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4c)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4c)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4c)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 4c) is provided. , 5, 10, 20, 30, 40 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, 5, 10, 20, 30, 40 or all of the polypeptides (or parts thereof) encoded by the drug susceptibility genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 4c) at least any 1, 5, 10, 20, 30, 40 or all drug sensitivity genes or RNA hybrids encoding them provided. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 4c) Combination of polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4d)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4d)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4d)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4d)提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 4d) is provided. , 5, 10, 20, 30, 40 or all drug susceptibility genes or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, 5, 10, 20, 30, 40 or all of the polypeptides (or parts thereof) encoded by the drug susceptibility genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 4d) at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided, or RNA hybrids encoded by them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 4d) Combining polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4e)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4e)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4e)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4e)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 4e) is provided. , 5, 10, 20, 30, 40, 50, 60, 70 or all drug susceptibility genes, or RNA hybrids encoding them. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits, each comprising a capture polypeptide molecule) configured to match at least any of 1 , 5, 10, 20, 30, 40, 50, 60, 70 or all of the polypeptides encoded by the drug susceptibility genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 4e) at least any 1, 5, 10, 20, 30, 40, 50, 60, 70 or all of the drug sensitivity genes or their encoded RNA hybrids provided. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 4e) Combining polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40, 50, 60, 70 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4f)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4f)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表4f)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表4f)提供的至少任意1、5、10、20、30、40、50、60、70個或所有藥物敏感性基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 4f) is provided. , 5, 10, 20, 30, 40, 50, 60, 70 or all drug susceptibility genes or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, , and 5, 10, 20, 30, 40, 50, 60, 70 or all of the polypeptides encoded by the drug susceptibility genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 4f) at least any 1, 5, 10, 20, 30, 40, 50, 60, 70 or all of the drug sensitivity genes or their encoded RNA hybrids provided. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 4f) Combining polypeptides (or parts thereof) encoded by at least any 1, 5, 10, 20, 30, 40, 50, 60, 70 or all of the drug sensitivity genes provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表5或6提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表5或6提供的至少任意1、5、10、20、30、40、50、100、200或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表5或6提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表5或6提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any of the molecules provided in Table 5 or 6 is provided. 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug resistance genes, or their encoded RNA hybrids. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least any one of the molecules provided in Table 5 or 6 is provided. , 5, 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by the drug-resistant genes. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with At least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the drug resistance genes provided in Table 5 or 6, or RNA hybrids encoded by them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table Combination of at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by drug resistance genes provided by 5 or 6.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，其包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any 1, Hybridization of 5, 10, 20, 30, 40, 50, 100, 200 or all drug resistance genes, or their encoded RNAs. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least any of 1, 5 provided in Table 7 is provided. , 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by the drug resistance gene are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured as in Table 7 Provided at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug resistance genes, or RNA hybrids encoded by them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match those provided in Table 7. At least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by the drug-resistant genes are combined.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7a)提供的至少任意1、5、10、20、30、40或所有耐藥基因或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7a)中提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7a)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，其包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7a)提供的至少任意1、5、10、20、30、40或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 7a) is provided. , 5, 10, 20, 30, 40 or all drug resistance genes or their encoded RNA hybrids. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any one of the molecules provided in Table 7a) is provided. , 5, 10, 20, 30, 40 or all of the polypeptides (or parts thereof) encoded by the drug resistance gene are combined. In some embodiments, there is provided a kit comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) configured as described in Table 7a ) provided at least any 1, 5, 10, 20, 30, 40 or all drug resistance genes, or RNA hybrids encoded by them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured as in Table 7a) Provided at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) are combined.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7b)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7b)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7b)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7b)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 7b) is provided. , 5, 10, 20, 30, 40 or all drug resistance genes, or RNA hybrids encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, 5, 10, 20, 30, 40 or all of the drug resistance gene encoded polypeptides (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 7b) at least any 1, 5, 10, 20, 30, 40 or all drug resistance genes provided, or RNA hybrids encoded by them. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured for use with a table 7b) Combination of at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) provided.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7c)提供的至少任意1、5、10、20、30個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7c)提供的至少任意1、5、10、20、30個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7c)提供的至少任意1、5、10、20、30個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，其包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7c)提供的至少任意1、5、10、20、30個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to match at least any one of the molecules provided in Table 7c) is provided. , 5, 10, 20, 30 or all drug resistance genes, or their encoded RNA hybrids. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any 1, 5, 10, 20, 30 or all polypeptides (or parts thereof) encoded by drug resistance genes are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) configured to interact with Table 7c) at least any 1, 5, 10, 20, 30 or all of the drug resistance genes provided, or RNA hybrids encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured as in Table 7c) Combination of at least any 1, 5, 10, 20, 30 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) provided.

在一些實施方案中，提供了多種捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，其被配置為與表7d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，其被配置為與表7d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，該捕獲核酸分子被配置為與表7d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，這些捕獲多肽分子被配置為與表7d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match at least any of the 1, , Hybridization of 5, 10, 20, 30, 40 or all drug resistance genes, or RNAs encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of 1, 5, 10, 20, 30, 40 or all of the drug resistance gene encoded polypeptides (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) configured to Hybridize with at least any 1, 5, 10, 20, 30, 40 or all of the drug resistance genes provided in Table 7d), or RNA encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to To combine with at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides (or parts thereof) encoded by the drug resistance genes provided in Table 7d).

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表7e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，該捕獲多肽分子被配置為與表7e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，該捕獲核酸分子被配置為與表7e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，其包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表7e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) are provided, said capture nucleic acid molecules being configured to match the values provided in Table 7e). At least any 1, 5, 10, 20, 30, 40, 50, 100 or all drug resistance genes or RNA hybrids encoded by them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits, each comprising a capture polypeptide molecule) configured to match at least one of the capture polypeptide molecules provided in Table 7e) is provided. Any 1, 5, 10, 20, 30, 40, 50, 100 or all of the polypeptides (or parts thereof) encoded by the drug resistance gene are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) configured to Hybridize with at least any 1, 5, 10, 20, 30, 40, 50, 100 or all of the drug resistance genes provided in Table 7e), or RNA encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to Combine with at least any 1, 5, 10, 20, 30, 40, 50, 100 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) provided in Table 7e).

在一些實施方案中，提供了多種捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表B提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA中的雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表B提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表B提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，其包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表B提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to interact with at least any of the compounds provided in Table B is provided. Hybridization in 1, 5, 10, 20, 30, 40 or all drug resistance genes, or RNAs encoding them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to match at least Any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the resistance genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) configured to To hybridize with at least any 1, 5, 10, 20, 30, 40 or all drug resistance genes provided in Table B, or RNA encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to Combine with at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) provided in Table B.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，其包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match those provided in Table 8 is provided. At least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all drug resistance genes, or RNAs encoded by them are hybridized. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least one of the molecules provided in Table 8 is provided. Any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all of the polypeptides encoded by the resistance genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) configured to To hybridize with at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all of the drug resistance genes provided in Table 8, or RNAs encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to Combine with at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all of the polypeptides (or parts thereof) encoded by the drug resistance genes provided in Table 8.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8a)提供的至少任意1、5、10、20、30、40、50個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其各自包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8a)提供的至少任意1、5、10、20、30、40、50個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8a)提供的至少任意1、5、10、20、30、40、50個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其各自包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8a)提供的至少任意1、5、10、20、30、40、50個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) are provided, said capture nucleic acid molecules being configured to match those provided in Table 8a). At least any 1, 5, 10, 20, 30, 40, 50 or all drug-resistant genes or RNA hybrids encoded by them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match at least any of the capture polypeptide molecules provided in Table 8a) is provided. 1, 5, 10, 20, 30, 40, 50 or all of the drug resistance gene encoded polypeptides (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that It is configured to hybridize with at least any 1, 5, 10, 20, 30, 40, 50 or all of the drug resistance genes provided in Table 8a), or the RNA encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to Combine with at least any 1, 5, 10, 20, 30, 40, 50 or all of the polypeptides (or parts thereof) encoded by the drug resistance genes provided in Table 8a).

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8b)提供的至少任意1、5、10、20、30、40、50個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8b)提供的至少任意1、5、10、20、30、40、50個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8b)提供的至少任意1、5、10、20、30、40、50個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，這些捕獲多肽分子被配置為與表8b)提供的至少任意1、5、10、20、30、40、50或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) are provided, said capture nucleic acid molecules being configured to match those provided in Table 8b). At least any 1, 5, 10, 20, 30, 40, 50 or all drug-resistant genes or RNA hybrids encoded by them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match those provided in Table 8b) are provided. At least any 1, 5, 10, 20, 30, 40, 50 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that It is configured to hybridize with at least any 1, 5, 10, 20, 30, 40, 50 or all of the drug resistance genes provided in Table 8b), or RNA encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured to To combine with at least any 1, 5, 10, 20, 30, 40, 50 or all of the polypeptides (or parts thereof) encoded by the drug-resistant genes provided in Table 8b).

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8c)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8c)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8c)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8c)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule) are provided, said capture nucleic acid molecules being configured in the same manner as provided in Table 8c). At least any 1, 5, 10, 20, 30, 40 or all drug-resistant genes or RNA hybrids encoded by them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to correspond to those provided in Table 8c) are provided. At least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that It is configured to hybridize with at least any 1, 5, 10, 20, 30, 40 or all of the drug resistance genes provided in Table 8c), or RNA encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by It is configured to combine with at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) provided in Table 8c).

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8d)提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) are provided, said capture nucleic acid molecules being configured to correspond to those provided in Table 8d). At least any 1, 5, 10, 20, 30, 40 or all drug-resistant genes or RNA hybrids encoded by them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to correspond to those provided in Table 8d) are provided. At least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that It is configured to hybridize with at least any 1, 5, 10, 20, 30, 40 or all of the drug resistance genes provided in Table 8d), or the RNA encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by It is configured to combine with at least any 1, 5, 10, 20, 30, 40 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) provided in Table 8d).

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表8e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因、或其編碼的RNA雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表8e)提供的至少任意1、5、10、20、30、40、50、100個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) are provided, said capture nucleic acid molecules being configured to correspond to those provided in Table 8e). At least any 1, 5, 10, 20, 30, 40, 50, 100 or all drug resistance genes or RNA hybrids encoded by them. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys, each comprising a capture polypeptide molecule) configured to match those provided in Table 8e) are provided. At least any 1, 5, 10, 20, 30, 40, 50, 100 or all of the polypeptides encoded by the resistance genes (or parts thereof) are combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that It is configured to hybridize with at least any 1, 5, 10, 20, 30, 40, 50, 100 or all of the drug resistance genes provided in Table 8e), or RNAs encoded by them. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by It is configured to combine with at least any 1, 5, 10, 20, 30, 40, 50, 100 or all of the polypeptides encoded by the drug resistance genes (or parts thereof) provided in Table 8e).

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表1提供的至少任意1、5、10、20、30個或所有藥物敏感性基因(或其編碼的RNA)以及表5提供的至少任意1、5、10、20、30或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表1提供的至少任意1、5、10、20個或所有藥物敏感性基因中的至少任何一個以及表5提供的至少任意1、5、10、20、30或所有耐藥基因中的至少任何一個編碼的多肽(或其部分)結合。在一些實施方案中，提供了套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表1提供的至少任意1、5、10、20個或所有藥物敏感性基因(或其編碼的RNA)以及表5提供的至少任意1、5、10、20、30或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表1提供的至少任意1、5、10、20個或所有藥物敏感性基因以及表5提供的至少任意1、5、10、20、30或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match those provided in Table 1 is provided. At least any 1, 5, 10, 20, 30 or all drug sensitivity genes (or their encoded RNAs) and at least any 1, 5, 10, 20, 30 or all of the drug resistance genes (or their encoded RNAs) provided in Table 5 RNA) hybridization. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least one of the molecules provided in Table 1 is provided. Any 1, 5, 10, 20 or at least any one of all drug-sensitivity genes and at least any 1, 5, 10, 20, 30 or at least any one of all drug-resistant genes provided in Table 5 coded polypeptide ( or part thereof) combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that are captured by Configured to be at least any 1, 5, 10, 20 or all of the drug-sensitive genes (or their encoded RNAs) provided in Table 1 and at least any of 1, 5, 10, 20, 30 or all of the drug-resistant genes provided in Table 5 Gene (or the RNA it encodes) hybridizes. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by Configured to be provided with at least any 1, 5, 10, 20 or all drug sensitivity genes provided in Table 1 and at least any 1, 5, 10, 20, 30 or all drug resistance gene encoding polypeptides provided in Table 5 (or their part) combined.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表1提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因(或其編碼的RNA)以及表6提供的至少任意1、5、10、20、30或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置與由表1提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因以及表6提供的至少任意1、5、10、20、30或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表1提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因(或其編碼的RNA)以及表6提供的至少任意1、5、10、20、30或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表1提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因以及表6提供的至少任意1、5、10、20、30個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match those provided in Table 1 is provided. At least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug susceptibility genes (or their encoded RNAs) and at least any 1, 5, 10, 20, 30 or All drug resistance genes (or their encoded RNAs) were hybridized. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) configured with at least one of the capture polypeptide molecules provided in Table 1 is provided. Any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug-sensitive genes and at least any 1, 5, 10, 20, 30 or all drug-resistant gene-encoded polypeptides provided in Table 6 ( or part thereof) combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that It is configured to provide at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug sensitivity genes (or RNA encoded by them) provided in Table 1 and at least any 1, 5, 10, 20, 30 or all drug resistance genes (or their encoded RNA) were hybridized. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by Configured to be at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug sensitivity genes provided in Table 1 and at least any 1, 5, 10, 20, 30 provided in Table 6 Or the combination of polypeptides (or parts thereof) encoded by all drug-resistant genes.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表2提供的至少任意1、5、10、20個或所有藥物敏感性基因(或其編碼的RNA)以及表6提供的至少任意1、5、10、20、30個或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表2提供的至少任意1、5、10、20個或所有藥物敏感性基因以及表6提供的至少任意1、5、10、20、30個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了套組，所述套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表2提供的至少任意1、5、10、20個或所有藥物敏感性基因(或其編碼的RNA)以及表6提供的至少任意1、5、10、20、30個或所有耐藥基因(或其編碼的 RNA)雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表2提供的至少任意1、5、10、20個或所有藥物敏感性基因以及表6提供的至少任意1、5、10、20、30個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match those provided in Table 2 is provided. At least any 1, 5, 10, 20 or all drug sensitivity genes (or their encoded RNAs) and at least any 1, 5, 10, 20, 30 or all of the drug resistance genes (or their encoded RNAs) provided in Table 6 RNA) hybridization. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least one of the molecules provided in Table 2 is provided. Combination of any 1, 5, 10, 20 or all of the drug-sensitive genes and at least any of 1, 5, 10, 20, 30 or all of the drug-resistant genes (or parts thereof) encoded by Table 6. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits, each comprising a capture nucleic acid molecule), the capture nucleic acid molecule Be configured to provide at least any 1, 5, 10, 20 or all drug sensitivity genes (or RNAs thereof) provided in Table 2 and at least any 1, 5, 10, 20, 30 or all provided in Table 6 Drug resistance gene (or its encoded RNA) hybridization. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by Configured to provide at least any 1, 5, 10, 20 or all drug sensitivity genes provided in Table 2 and at least any 1, 5, 10, 20, 30 or all drug resistance gene coding polypeptides provided in Table 6 (or part of it) combined.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表3提供的至少任意1、5、10、20、30、40、50、100、200個、或所有藥物敏感性基因(或其編碼的RNA)以及表7提供的至少任意1、5、10、20、30、40、50、100、200個、或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表3提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因以及表7提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，其包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表3提供的至少任意1、5、10、20、30、40、50、100、200個、或所有藥物敏感性基因(或其編碼的RNA)以及或表7提供的至少任意1、5、10、20、30、40、50、100、200個、或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表3提供的至少任意1、5、10、20、30、40、50、100、200個或所有藥物敏感性基因以及表7提供的至少任意1、5、10、20、30、40、50、100、200個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match the At least any 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitivity genes (or RNA encoded by them) and at least any 1, 5, 10, 20, 30 provided in Table 7 , 40, 50, 100, 200, or all drug resistance genes (or their encoded RNAs) are hybridized. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least one of the molecules provided in Table 3 is provided. Any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug sensitivity genes and at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 provided in Table 7 Or the combination of polypeptides (or parts thereof) encoded by all drug-resistant genes. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) configured to For at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 provided in Table 3, or all drug sensitivity genes (or RNA encoded by them) and or at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistance genes (or their encoded RNAs) are hybridized. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by Configured to be at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all drug sensitivity genes provided in Table 3 and at least any 1, 5, 10, 20, 30, 40, 50, 100, 200 or all of the polypeptides (or parts thereof) encoded by the resistance gene are combined.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表A提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因(或其編碼的RNA)以及或表B提供的至少任意1、5、10、20、30、40個或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表A提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因以及表B提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，該套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表A提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因(或其編碼的RNA)以及或表B提供的至少任意1、5、10、20、30、40或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表A提供的至少任意1、5、10、20、30、40個或所有藥物敏感性基因以及表B提供的至少任意1、5、10、20、30、40個或所有耐藥基因編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match those provided in Table A is provided. At least any 1, 5, 10, 20, 30, 40 or all drug susceptibility genes (or their encoded RNAs) and or at least any 1, 5, 10, 20, 30, 40 or all resistance genes provided in Table B Drug gene (or its encoded RNA) hybridization. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least Any 1, 5, 10, 20, 30, 40 or all drug-susceptibility genes and at least any 1, 5, 10, 20, 30, 40 or all drug-resistant gene-encoded polypeptides (or parts thereof) provided in Table B ) combined. In some embodiments, a kit is provided comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule) that Configured to be at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes (or their encoded RNAs) provided in Table A and or at least any 1, 5, 10, 20 provided in Table B , 30, 40 or all drug resistance genes (or their encoded RNA) hybridization. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by Configured with at least any 1, 5, 10, 20, 30, 40 or all of the drug sensitivity genes provided in Table A and at least any of 1, 5, 10, 20, 30, 40 or all of the drug resistance genes provided in Table B Gene-encoded polypeptide (or part thereof) binding.

在一些實施方案中，提供了多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有藥物敏感性基因(或其編碼的RNA)以及表8提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有藥物敏感性基因以及表8提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因所編碼的多肽(或其部分)結合。在一些實施方案中，提供了一種套組，所述套組包含多個捕獲核酸分子(或探針、引子、寡核苷酸或誘餌，其每個都包含捕獲核酸分子)，所述捕獲核酸分子被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200、300、或所有藥物敏感性基因(或其編碼的RNA)以及表8中提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因(或其編碼的RNA)雜交。在一些實施方案中，提供了一種套組，該套組包含多個捕獲多肽分子(例如，多肽、抗體或其片段、或誘餌，其每個都包含捕獲多肽分子)，所述捕獲多肽分子被配置為與表4提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有藥物敏感性基因以及表8提供的至少任意1、5、10、20、30、40、50、100、200、300個或所有耐藥基因所編碼的多肽(或其部分)結合。In some embodiments, a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits, each comprising a capture nucleic acid molecule) configured to match those provided in Table 4 is provided. At least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all drug sensitivity genes (or RNA encoded by them) and at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all drug resistance genes (or their encoded RNAs) were hybridized. In some embodiments, a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or baits each comprising a capture polypeptide molecule) configured to match at least one of the molecules provided in Table 4 is provided. Any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all drug sensitivity genes and at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all of the polypeptides (or parts thereof) encoded by the drug resistance genes are combined. In some embodiments, there is provided a kit comprising a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides or baits each comprising a capture nucleic acid molecule), the capture nucleic acid Molecules are configured with at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 provided in Table 4, or all drug sensitivity genes (or RNAs encoded thereof) and provided in Table 8. At least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all of the drug resistance genes (or their encoded RNAs) are hybridized. In some embodiments, a kit is provided comprising a plurality of capture polypeptide molecules (e.g., polypeptides, antibodies or fragments thereof, or decoys each comprising a capture polypeptide molecule) that are captured by Configured to provide at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all drug sensitivity genes provided in Table 4 and at least any 1, 5, 10, 20, 30, 40, 50, 100, 200, 300 or all of the polypeptides encoded by the resistance genes (or parts thereof) are combined.

誘餌bait

本文提供了適合於偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)或用於增濃一個或多個藥物敏感性基因和/或耐藥基因的誘餌。Provided herein are suitable for detecting one or more drug sensitivity abnormalities (such as drug sensitivity mutations) and/or drug resistance abnormalities (such as drug resistance mutations) of the present application or for enriching one or more drug sensitivity genes and and/or decoys for drug resistance genes.

在一些實施方案中，所述誘餌包含捕獲多肽分子，其被配置為與靶多肽或其片段或部分結合。在一些實施方案中，所述片段的長度包含(或為)至少約5個胺基酸。在一些實施方案中，所述捕獲多肽分子是多肽(例如，由藥物敏感性基因/耐藥基因編碼的受體的配位體)。在一些實施方案中，所述捕獲多肽分子是抗體或其抗原結合片段。在一些實施方案中，所述捕獲多肽分子的長度為至少約10個胺基酸，例如至少約15個胺基酸、20個胺基酸、30個胺基酸、40個胺基酸、50個胺基酸、100個胺基酸、1000個胺基酸或更長。In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a target polypeptide or fragment or portion thereof. In some embodiments, the fragment comprises (or is) at least about 5 amino acids in length. In some embodiments, the capture polypeptide molecule is a polypeptide (eg, a ligand for a receptor encoded by a drug sensitivity/resistance gene). In some embodiments, the capture polypeptide molecule is an antibody or antigen-binding fragment thereof. In some embodiments, the capture polypeptide molecule is at least about 10 amino acids in length, such as at least about 15 amino acids, 20 amino acids, 30 amino acids, 40 amino acids, 50 amino acids, 100 amino acids, 1000 amino acids or longer.

在一些實施方案中，所述誘餌包含捕獲核酸分子，所述捕獲核酸分子被配置為與靶核酸分子或其片段或部分雜交。在一些實施方案中，所述片段包含(或為)約5至約25個核苷酸、約5至約300個核苷酸、約100至約300個核苷酸、約130至約230個核苷酸、或約150至約200個核苷酸。In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to a target nucleic acid molecule or a fragment or portion thereof. In some embodiments, the fragment comprises (or is) about 5 to about 25 nucleotides, about 5 to about 300 nucleotides, about 100 to about 300 nucleotides, about 130 to about 230 nucleotides nucleotides, or about 150 to about 200 nucleotides.

在一些實施方案中，所述捕獲核酸分子為約5至約25個核苷酸，約5至約300個核苷酸，約100至約300個核苷酸，約130至約230個核苷酸，或約150至約200個核苷酸。在一些實施方案中，所述片段的長度包含(或為)約100個核苷酸、約125個核苷酸、約150個核苷酸、約175個核苷酸、約200個核苷酸、約225個核苷酸、約250個核苷酸、約275個核苷酸或約300個核苷酸。在一些實施方案中，所述捕獲核酸分子的長度包含(或為)約100個核苷酸、約125個核苷酸、約150個核苷酸、約175個核苷酸、約200個核苷酸、約225個核苷酸、約250個核苷酸、約275個核苷酸或約300個核苷酸。在一些實施方案中，所述捕獲核酸分子的長度為約100個核苷酸、約125個核苷酸、約150個核苷酸、約175個核苷酸、約200個核苷酸、約225個核苷酸、約250個核苷酸、約275個核苷酸或約300個核苷酸。在一些實施方案中，所述捕獲核酸分子的長度為約5至約25個核苷酸、約5至約300個核苷酸、約100至約300個核苷酸、約130至約230個核苷酸，或約150至約200個核苷酸。In some embodiments, the capture nucleic acid molecule is about 5 to about 25 nucleotides, about 5 to about 300 nucleotides, about 100 to about 300 nucleotides, about 130 to about 230 nucleosides acid, or about 150 to about 200 nucleotides. In some embodiments, the fragment comprises (or is) about 100 nucleotides, about 125 nucleotides, about 150 nucleotides, about 175 nucleotides, about 200 nucleotides in length , about 225 nucleotides, about 250 nucleotides, about 275 nucleotides, or about 300 nucleotides. In some embodiments, the length of the capture nucleic acid molecule comprises (or is) about 100 nucleotides, about 125 nucleotides, about 150 nucleotides, about 175 nucleotides, about 200 nuclei nucleotides, about 225 nucleotides, about 250 nucleotides, about 275 nucleotides, or about 300 nucleotides. In some embodiments, the capture nucleic acid molecule is about 100 nucleotides, about 125 nucleotides, about 150 nucleotides, about 175 nucleotides, about 200 nucleotides, about 225 nucleotides, about 250 nucleotides, about 275 nucleotides, or about 300 nucleotides. In some embodiments, the capture nucleic acid molecule is about 5 to about 25 nucleotides, about 5 to about 300 nucleotides, about 100 to about 300 nucleotides, about 130 to about 230 nucleotides in length. nucleotides, or about 150 to about 200 nucleotides.

在一些實施方案中，所述捕獲核酸分子是DNA、RNA或DNA/RNA分子。In some embodiments, the capture nucleic acid molecule is a DNA, RNA, or DNA/RNA molecule.

在一些實施方案中，本文提供的誘餌包含DNA、RNA或DNA/RNA分子。在一些實施方案中，本文提供的誘餌包含多肽、或抗體或其抗原結合片段。在一些實施方案中，本文提供的誘餌包括標記或標籤。在一些實施方案中，標記或標籤是放射性標記、螢光標記、酶標記、序列標記、生物素或另一種配位體。在一些實施方案中，本文提供的誘餌包含偵測試劑例如螢光標記物。在一些實施方案中，本文提供的誘餌包含(例如，綴合到)親和標籤，例如，其允許捕獲和單離由誘餌和與誘餌雜交的核酸形成的雜合體。在一些實施方案中，親和標籤是抗體、抗體片段、生物素或業內已知的任何其他合適的親和標籤或試劑。在一些實施方案中，所述誘餌適用於液相雜交。In some embodiments, the baits provided herein comprise DNA, RNA or DNA/RNA molecules. In some embodiments, the baits provided herein comprise polypeptides, or antibodies or antigen-binding fragments thereof. In some embodiments, the baits provided herein include markers or tags. In some embodiments, the label or tag is a radioactive label, a fluorescent label, an enzyme label, a sequence label, biotin, or another ligand. In some embodiments, the baits provided herein comprise detection reagents such as fluorescent markers. In some embodiments, a bait provided herein comprises (eg, is conjugated to) an affinity tag, eg, which allows capture and isolation of a hybrid formed by the bait and a nucleic acid that hybridizes to the bait. In some embodiments, the affinity tag is an antibody, antibody fragment, biotin, or any other suitable affinity tag or reagent known in the art. In some embodiments, the bait is suitable for liquid phase hybridization.

所述誘餌可以根據業內已知的方法生產和使用，例如，如WO2012092426A1和/或Frampton et al (2013) Nat Biotechnol, 31:1023-1031中所述，其藉由引用併入本文。例如，可以藉由獲得最初在微陣列上合成的合成長寡核苷酸池並擴增寡核苷酸以產生誘餌序列來生產生物素化的誘餌(例如，RNA誘餌)。在一些實施方案中，藉由在誘餌序列的一端添加RNA聚合酶啟動子序列並使用RNA聚合酶合成RNA序列來產生誘餌。在一個實施方案中，合成寡去氧核苷酸文庫可以從商業供應商處獲得，例如Agilent Technologies, Inc.，並使用已知的核酸擴增方法進行擴增。任意合適的蛋白質(例如抗體)合成方法都可以在本文中用於生產誘餌。The bait can be produced and used according to methods known in the art, for example, as described in WO2012092426A1 and/or Frampton et al (2013) Nat Biotechnol, 31:1023-1031, which are incorporated herein by reference. For example, biotinylated baits (eg, RNA baits) can be produced by obtaining a pool of synthetic long oligonucleotides initially synthesized on a microarray and amplifying the oligonucleotides to generate bait sequences. In some embodiments, the bait is produced by adding an RNA polymerase promoter sequence to one end of the bait sequence and using the RNA polymerase to synthesize the RNA sequence. In one embodiment, synthetic oligodeoxynucleotide libraries can be obtained from commercial suppliers, such as Agilent Technologies, Inc., and amplified using known nucleic acid amplification methods. Any suitable method of protein (eg, antibody) synthesis can be used herein to produce baits.

在一些實施方案中，本文提供的誘餌的長度至少約為10個胺基酸。在一些實施方案中，本文提供的誘餌包含靶特異性誘餌序列(例如本文所述的捕獲多肽分子)及在每一端的通用尾。在一些實施方案中，靶特異性序列，例如本文所述的捕獲多肽分子，長度至少約10個胺基酸，例如至少約15個胺基酸、20個胺基酸、30個胺基酸、40個胺基酸、50個胺基酸、100個胺基酸、1000個胺基酸或更長。In some embodiments, the baits provided herein are at least about 10 amino acids in length. In some embodiments, a bait provided herein comprises a target-specific bait sequence (eg, a capture polypeptide molecule described herein) and a universal tail at each end. In some embodiments, the target-specific sequence, e.g., a capture polypeptide molecule described herein, is at least about 10 amino acids in length, e.g., at least about 15 amino acids, 20 amino acids, 30 amino acids, 40 amino acids, 50 amino acids, 100 amino acids, 1000 amino acids or longer.

在一些實施方案中，本文提供的誘餌在約100個核苷酸和約300個核苷酸之間。在一些實施方案中，本文提供的誘餌在約130個核苷酸和約230個核苷酸之間。在一些實施方案中，本文提供的誘餌在約150個核苷酸和約200個核苷酸之間。在一些實施方案中，本文提供的誘餌包含靶特異性誘餌序列(例如本文所述的捕獲核酸分子)及在每一端的通用尾。在一些實施方案中，靶特異性序列，例如本文所述的捕獲核酸分子，介於約10個核苷酸和約300個核苷酸之間。在一些實施方案中，靶特異性序列，例如本文所述的捕獲核酸分子，介於約100個核苷酸和約200個核苷酸之間。在一些實施方案中，靶特異性序列，例如本文所述的捕獲核酸分子，介於約120個核苷酸和約170個核苷酸之間。在一些實施方案中，靶特異性序列，例如本文所述的捕獲核酸分子，為約150個核苷酸或約170個核苷酸。在一些實施方案中，本文提供的誘餌包括包含約200個核苷酸的寡核苷酸，其中約150個核苷酸或約170個核苷酸是靶特異性的(例如本文所述的捕獲核酸分子)，以及其他50個核苷酸或30個核苷酸(例如，在誘餌每個末端的25個或15個核苷酸)是（例如，適用於PCR擴增的）通用的任意尾。In some embodiments, the baits provided herein are between about 100 nucleotides and about 300 nucleotides. In some embodiments, the baits provided herein are between about 130 nucleotides and about 230 nucleotides. In some embodiments, the baits provided herein are between about 150 nucleotides and about 200 nucleotides. In some embodiments, a bait provided herein comprises a target-specific bait sequence (eg, a capture nucleic acid molecule described herein) and a universal tail at each end. In some embodiments, a target-specific sequence, such as a capture nucleic acid molecule described herein, is between about 10 nucleotides and about 300 nucleotides. In some embodiments, a target-specific sequence, such as a capture nucleic acid molecule described herein, is between about 100 nucleotides and about 200 nucleotides. In some embodiments, a target-specific sequence, such as a capture nucleic acid molecule described herein, is between about 120 nucleotides and about 170 nucleotides. In some embodiments, a target-specific sequence, such as a capture nucleic acid molecule described herein, is about 150 nucleotides or about 170 nucleotides. In some embodiments, the baits provided herein comprise oligonucleotides comprising about 200 nucleotides, of which about 150 nucleotides or about 170 nucleotides are target-specific (e.g., the capture nucleic acid molecule), and the other 50 nucleotides or 30 nucleotides (e.g., 25 or 15 nucleotides at each end of the bait) are universal arbitrary tails (e.g., suitable for PCR amplification) .

探針probe

本文還提供了探針，例如核酸分子，其適用於偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。在一些實施方案中，本文提供的探針包含被配置為與靶核酸分子雜交的核酸序列，所述靶核酸分子包含本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)或其片段或部分。Also provided herein are probes, eg, nucleic acid molecules, suitable for detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) and/or drug resistance abnormalities (eg, drug resistance mutations) of the present application. In some embodiments, the probes provided herein comprise a nucleic acid sequence configured to hybridize to a target nucleic acid molecule comprising one or more drug susceptibility abnormalities (e.g., drug susceptibility mutations) and/or Drug resistance abnormalities (such as drug resistance mutations) or fragments or parts thereof.

在一些實施方案中，所述探針包含核酸分子（DNA、RNA或DNA/RNA分子）。在一些實施方案中，所述探針包含核酸分子，所述核酸分子包含約10至約20個核苷酸、約12至約20個核苷酸、約10至約1000個核苷酸、約50至約500個核苷酸、約100至約500個核苷酸、約100至約300個核苷酸、約130至約230個核苷酸或約150至約200個核苷酸中的任一種。在一些實施方案中，所述探針包含核酸分子，所述核酸分子包含10個核苷酸、11個核苷酸、12個核苷酸、13個核苷酸、14個核苷酸、15個核苷酸、16個核苷酸、17個核苷酸、18個核苷酸、19個核苷酸、20個核苷酸、21個核苷酸、22個核苷酸、23個核苷酸、24個核苷酸、25個核苷酸、26個核苷酸、27個核苷酸、28個核苷酸、29個核苷酸或30個核苷酸中的任一種。在一些實施方案中，探針包含核酸分子，所述核酸分子包含約40個核苷酸至約50個核苷酸、約50個核苷酸至約100個核苷酸、約100個核苷酸至約150個核苷酸、約150個核苷酸至約200個核苷酸、約200個核苷酸至約250個核苷酸、約250個核苷酸至約300個核苷酸、約300個核苷酸至約350個核苷酸、約350個核苷酸至約400個核苷酸、約400個核苷酸至約450個核苷酸、約450個核苷酸至約500個核苷酸、約500個核苷酸至約550個核苷酸、約550個核苷酸至約600個核苷酸、約600個核苷酸至約650個核苷酸、約650個核苷酸至約700個核苷酸、約700個核苷酸至約750個核苷酸、約750個核苷酸至約800個核苷酸、約800個核苷酸至約850個核苷酸、約850個核苷酸至約900個核苷酸、約900個核苷酸至約950個核苷酸、或約950個核苷酸至約1000個核苷酸中的任一種。在一些實施方案中，所述探針包括含有約12至約20個核苷酸的核酸分子。In some embodiments, the probes comprise nucleic acid molecules (DNA, RNA, or DNA/RNA molecules). In some embodiments, the probe comprises a nucleic acid molecule comprising about 10 to about 20 nucleotides, about 12 to about 20 nucleotides, about 10 to about 1000 nucleotides, about 50 to about 500 nucleotides, about 100 to about 500 nucleotides, about 100 to about 300 nucleotides, about 130 to about 230 nucleotides, or about 150 to about 200 nucleotides any kind. In some embodiments, the probe comprises a nucleic acid molecule comprising 10 nucleotides, 11 nucleotides, 12 nucleotides, 13 nucleotides, 14 nucleotides, 15 Nucleotides, 16 Nucleotides, 17 Nucleotides, 18 Nucleotides, 19 Nucleotides, 20 Nucleotides, 21 Nucleotides, 22 Nucleotides, 23 Nucleotides Any of nucleotides, 24 nucleotides, 25 nucleotides, 26 nucleotides, 27 nucleotides, 28 nucleotides, 29 nucleotides or 30 nucleotides. In some embodiments, the probe comprises a nucleic acid molecule comprising about 40 nucleotides to about 50 nucleotides, about 50 nucleotides to about 100 nucleotides, about 100 nucleosides acid to about 150 nucleotides, about 150 nucleotides to about 200 nucleotides, about 200 nucleotides to about 250 nucleotides, about 250 nucleotides to about 300 nucleotides , about 300 nucleotides to about 350 nucleotides, about 350 nucleotides to about 400 nucleotides, about 400 nucleotides to about 450 nucleotides, about 450 nucleotides to about 500 nucleotides, about 500 nucleotides to about 550 nucleotides, about 550 nucleotides to about 600 nucleotides, about 600 nucleotides to about 650 nucleotides, about 650 nucleotides to about 700 nucleotides, about 700 nucleotides to about 750 nucleotides, about 750 nucleotides to about 800 nucleotides, about 800 nucleotides to about 850 nucleotides, from about 850 nucleotides to about 900 nucleotides, from about 900 nucleotides to about 950 nucleotides, or from about 950 nucleotides to about 1000 nucleotides A sort of. In some embodiments, the probes comprise nucleic acid molecules comprising about 12 to about 20 nucleotides.

在一些實施方案中，本文提供的探針包括標記或標籤。在一些實施方案中，標記或標籤是放射性標記(例如放射性同位素)、螢光標記(例如螢光化合物)、酶標記、酶輔因數、序列標籤、生物素或另一種配位體。在一些實施方案中，本文提供的探針包含偵測試劑，例如螢光標記物。在一些實施方案中，本文提供的探針包含(例如綴合到)親和標籤，例如，其允許捕獲和單離由探針和與探針雜交的核酸形成的雜合體。在一些實施方案中，所述親和標籤是抗體、抗體片段、生物素或業內已知的任何其他合適的親和標籤或試劑。在一些實施方案中，所述探針適用於液相雜交。In some embodiments, the probes provided herein include labels or labels. In some embodiments, the label or label is a radiolabel (eg, a radioisotope), a fluorescent label (eg, a fluorescent compound), an enzyme label, an enzyme cofactor, a sequence tag, biotin, or another ligand. In some embodiments, the probes provided herein comprise detection reagents, such as fluorescent labels. In some embodiments, the probes provided herein comprise (eg, are conjugated to) an affinity tag, eg, which permits capture and isolation of hybrids formed by the probe and nucleic acid to which the probe hybridizes. In some embodiments, the affinity tag is an antibody, antibody fragment, biotin, or any other suitable affinity tag or reagent known in the art. In some embodiments, the probe is suitable for liquid phase hybridization.

在一些實施方案中，本文提供的一種或多種探針適用於（例如，如上所述的）原位雜交法，例如FISH。In some embodiments, one or more probes provided herein are suitable for use in (eg, as described above) in situ hybridization methods, such as FISH.

染色體探針，例如，用於本文所述的FISH方法中，通常長度為約50至約105個核苷酸。較長的探針通常包含約100至約500個核苷酸的較小片段。與著絲粒DNA和基因座特異性DNA雜交的探針可商購獲得，例如從Vysis, Inc. (Downers Grove, IL)、Molecular Probes, Inc. (Eugene, Oreg.)或從Cytocell (Oxfordshire, UK)獲得。或者，可以藉由準則技術從染色體或基因組DNA非商業化地製造探針。例如，可以使用的DNA來源包括基因組DNA、克隆的DNA序列、包含染色體(例如人類染色體)或染色體(例如人類染色體)的部分以及主體的正常染色體互補體的體細胞雜交體，以及藉由流式細胞術或顯微切割純化的染色體。可以藉由克隆或藉由PCR的位點特異性擴增來單離目的區域。本申請的探針還可以與RNA分子例如mRNA雜交。Chromosomal probes, eg, for use in the FISH methods described herein, are typically about 50 to about 105 nucleotides in length. Longer probes generally comprise smaller fragments of about 100 to about 500 nucleotides. Probes that hybridize to centromere DNA and locus-specific DNA are commercially available, for example, from Vysis, Inc. (Downers Grove, IL), Molecular Probes, Inc. (Eugene, Oreg.) or from Cytocell (Oxfordshire, IL). UK) obtained. Alternatively, probes can be produced non-commercially from chromosomal or genomic DNA by standard techniques. For example, DNA sources that can be used include genomic DNA, cloned DNA sequences, somatic cell hybrids comprising chromosomes (eg, human chromosomes) or portions of chromosomes (eg, human chromosomes) and the normal chromosomal complement of the subject, and by flow cytometry Chromosomes purified by cytometry or microdissection. The region of interest can be isolated by cloning or by site-specific amplification by PCR. The probes of the present application can also hybridize to RNA molecules such as mRNA.

在一些實施方案中，探針，例如用於本文所述的FISH方法的探針，被標記為使得可以偵測到染色體區域或RNA上與探針雜交的區域。所述探針通常直接用螢光基團標記，允許探針在沒有輔助偵測分子的情況下視覺化。探針也可以藉由缺口平移、隨機引子標記或PCR標記來標記。可以使用螢光(直接)或半抗原(間接)標記的核苷酸來完成標記。代表性但非限制性的標記示例包括：AMCA-6-dUTP、CascadeBlue-4-dUTP、螢光素-12-dUTP、若丹明-6-dUTP、德州紅-6-dUTP、Cy3-6-dUTP、Cy5-dUTP、生物素 (BIO)-11-dUTP、地高辛 (DIG)-11-dUTP和二硝基苯基 (DNP)-11-dUTP。探針也可以用生物素或洋地黃毒苷間接標記，或用放射性同位素如32P和3H標記，並使用二級偵測分子，或進行進一步處理，以使探針視覺化。例如，用生物素標記的探針可以藉由與可偵測標記綴合的親和素來偵測，例如，親和素可以與酶標記物例如鹼性磷酸酶或辣根過氧化物酶綴合。可以使用酶的受質和/或觸媒在準則比色反應中偵測酶標記物。鹼性磷酸酶的觸媒包括5-溴-4-氯-3-磷酸吲哚和硝基藍四唑。二胺基苯甲酸酯可用作辣根過氧化物酶的觸媒。還可以製備探針，使得在探針與其靶標雜交後添加螢光或其他標記，以偵測與靶標雜交的探針。例如，可以使用將抗原分子摻入核苷酸序列中的探針。雜交後，偵測這些抗原分子，例如使用與抗原分子反應的特異性抗體。例如，此類抗體本身可以摻入螢光染料，或者可以使用具有結合的螢光染料的第二抗體來偵測。對於螢光探針，例如，用於FISH技術的螢光探針，可以使用為每個螢光團配備適當濾光片的螢光顯微鏡觀察螢光，或使用雙帶或三帶通濾光片組觀察多個螢光基團。或者，可以使用流式細胞術等技術來偵測染色體探針的雜交模式。In some embodiments, probes, such as those used in the FISH methods described herein, are labeled such that regions of the chromosome or RNA to which the probe hybridizes can be detected. The probes are usually directly labeled with a fluorophore, allowing visualization of the probe without auxiliary detection molecules. Probes can also be labeled by nick translation, random primer labeling, or PCR labeling. Labeling can be accomplished using fluorescent (direct) or hapten (indirect) labeled nucleotides. Representative but non-limiting examples of markers include: AMCA-6-dUTP, CascadeBlue-4-dUTP, Luciferin-12-dUTP, Rhodamine-6-dUTP, Texas Red-6-dUTP, Cy3-6- dUTP, Cy5-dUTP, Biotin (BIO)-11-dUTP, Digoxigenin (DIG)-11-dUTP and Dinitrophenyl (DNP)-11-dUTP. Probes can also be labeled indirectly with biotin or digoxigenin, or with radioactive isotopes such as 32P and 3H, and used with secondary detection molecules, or further processed to allow visualization of the probe. For example, a biotin-labeled probe can be detected by avidin conjugated to a detectable label, eg, avidin can be conjugated to an enzyme label such as alkaline phosphatase or horseradish peroxidase. Enzyme labels can be detected in standard colorimetric reactions using substrates and/or catalysts for the enzyme. Catalysts for alkaline phosphatase include indole 5-bromo-4-chloro-3-phosphate and nitro blue tetrazolium. Diaminobenzoate can be used as a catalyst for horseradish peroxidase. Probes can also be prepared such that after hybridization of the probe to its target a fluorescent or other label is added to detect probes hybridized to the target. For example, probes that incorporate antigenic molecules into the nucleotide sequence can be used. After hybridization, these antigenic molecules are detected, for example, using specific antibodies reactive with the antigenic molecules. For example, such antibodies can themselves incorporate a fluorescent dye, or can be detected using a secondary antibody with a fluorescent dye bound. For fluorescent probes, such as those used in FISH techniques, fluorescence can be observed using a fluorescent microscope equipped with appropriate filters for each fluorophore, or using double-band or triple-bandpass filters Groups observe multiple fluorophores. Alternatively, techniques such as flow cytometry can be used to detect hybridization patterns of chromosomal probes.

寡核苷酸Oligonucleotides

在一些態樣，本文提供了寡核苷酸，例如，作為引子使用。在一些實施方案中，本文提供的寡核苷酸（例如引子）包含被配置為與靶核酸分子雜交的核苷酸序列，所述靶核酸分子包含本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)或其片段或部分。在一些實施方案中，所述異常包括異常表達水準。在一些實施方案中，所述異常包括異常修飾。In some aspects, oligonucleotides are provided herein, eg, for use as primers. In some embodiments, an oligonucleotide provided herein (eg, a primer) comprises a nucleotide sequence configured to hybridize to a target nucleic acid molecule comprising one or more drug susceptibility disorders of the present application (eg, drug susceptibility mutations) and/or drug resistance abnormalities (such as drug resistance mutations) or fragments or parts thereof. In some embodiments, the abnormality comprises abnormal expression levels. In some embodiments, the abnormality comprises an abnormal modification.

在一些實施方案中，本文提供的寡核苷酸（例如引子）可用於藉由PCR啟動DNA合成或定序方法。在一些實施方案中，寡核苷酸可用於（例如使用PCR）擴增包含本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)或其片段(例如已知含有突變)的核酸分子。在一些實施方案中，寡核苷酸可用於對包含本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)或其片段的核酸分子進行定序。In some embodiments, oligonucleotides (eg, primers) provided herein can be used to initiate DNA synthesis or sequencing methods by PCR. In some embodiments, oligonucleotides can be used (e.g., using PCR) to amplify (e.g., using PCR) a drug-sensitivity abnormality (e.g., a drug-sensitivity mutation) and/or a drug-resistance abnormality (e.g., a drug-resistance mutation) or A nucleic acid molecule that is a fragment (eg, known to contain a mutation). In some embodiments, oligonucleotides can be used to detect nucleic acid molecules comprising one or more drug sensitivity aberrations (e.g., drug sensitivity mutations) and/or drug resistance aberrations (e.g., drug resistance mutations) of the present application, or fragments thereof. Sequencing.

在一些實施方案中，本文提供了寡核苷酸對，例如引子對，所述寡核苷酸對被配置為與包含本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的核酸分子或其片段雜交。在一些實施方案中，本申請的一對寡核苷酸可用於指導核酸分子或其片段的（例如使用PCR反應）擴增，所述核酸分子或其片段包含本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。In some embodiments, provided herein are pairs of oligonucleotides, such as pairs of primers, configured to be compatible with one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) comprising the present application and/or Or a nucleic acid molecule or a fragment thereof with abnormal drug resistance (such as a drug resistance mutation) hybridizes. In some embodiments, a pair of oligonucleotides of the present application can be used to direct amplification (e.g., using a PCR reaction) of a nucleic acid molecule or fragment thereof comprising one or more drug-sensitive compounds of the present application. Abnormalities (such as drug sensitivity mutations) and/or resistance abnormalities (such as drug resistance mutations).

在一些實施方案中，本文提供的寡核苷酸例如引子是單鏈核酸分子，例如用於定序或擴增方法。在一些實施方案中，本文提供的寡核苷酸是雙鏈核酸分子。在一些實施方案中，在（例如在定序或擴增方法中）使用之前對雙鏈寡核苷酸進行處理(例如變性)以使其兩條鏈單離。本文提供的寡核苷酸包含足夠長的核苷酸序列以與其靶標雜交並（例如在PCR或定序期間）引發延伸產物的合成。In some embodiments, oligonucleotides provided herein, eg, primers, are single-stranded nucleic acid molecules, eg, for use in sequencing or amplification methods. In some embodiments, the oligonucleotides provided herein are double-stranded nucleic acid molecules. In some embodiments, double-stranded oligonucleotides are treated (eg, denatured) to separate their two strands prior to use (eg, in a sequencing or amplification method). The oligonucleotides provided herein comprise nucleotide sequences long enough to hybridize to their targets and prime (eg, during PCR or sequencing) the synthesis of extension products.

在一些實施方案中，本文提供的寡核苷酸例如引子包含5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、88、89、90、91、92、93、94、95、96、97、98、99、100或更多個去氧核醣核苷酸或核醣核苷酸。在一些實施方案中，本文提供的寡核苷酸包含至少約8、10、15、20或30個去氧核醣核苷酸或核醣核苷酸中的任一種。在一些實施方案中，本文提供的寡核苷酸包含約10至約30個去氧核醣核苷酸或核醣核苷酸。在一些實施方案中，本文提供的寡核苷酸包含約10至約25個去氧核醣核苷酸或核醣核苷酸，包括例如約10至約20、約10至約15、約12至約20、或約17至約20個去氧核醣核苷酸或核醣核苷酸。在一些實施方案中，本文提供的寡核苷酸的長度和核苷酸序列是根據業內已知的方法確定的，例如基於諸如特定應用(例如PCR、定序文庫製備、定序)、反應條件(例如、緩衝液、溫度)、以及寡核苷酸的核苷酸序列或其靶標互補序列的核苷酸組成。In some embodiments, oligonucleotides provided herein, e.g., primers, comprise 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more deoxyribonucleotides or ribonucleotides. In some embodiments, an oligonucleotide provided herein comprises at least about any of 8, 10, 15, 20, or 30 deoxyribonucleotides or ribonucleotides. In some embodiments, the oligonucleotides provided herein comprise from about 10 to about 30 deoxyribonucleotides or ribonucleotides. In some embodiments, the oligonucleotides provided herein comprise from about 10 to about 25 deoxyribonucleotides or ribonucleotides, including, for example, from about 10 to about 20, from about 10 to about 15, from about 12 to about 20, or about 17 to about 20 deoxyribonucleotides or ribonucleotides. In some embodiments, the length and nucleotide sequence of the oligonucleotides provided herein are determined according to methods known in the art, e.g., based on factors such as the specific application (e.g., PCR, sequencing library preparation, sequencing), reaction conditions, (eg, buffer, temperature), and the nucleotide sequence of the oligonucleotide or the nucleotide composition of its target complement.

核酸或多肽樣本Nucleic acid or peptide samples

多種材料(例如組織)可作為本文提供的方法中使用的核酸(例如DNA或 RNA)或多肽樣本的來源。例如，所述樣本的來源可以是來自新鮮、冷凍和/或保藏的器官、組織樣本、活檢、切除、塗片或抽出物的實體組織；血液或任何血液成分；體液，例如腦脊液、羊水、尿液、唾液、痰液、腹膜液或間質液；或妊娠或個體發育中任何時間的細胞。在一些實施方案中，所述樣本來源是血液或血液成分。在一些實施方案中，所述樣本來源是腫瘤樣本，例如結腸癌樣本。在一些實施方案中，所述樣本是或包含生物組織或液體。在一些實施方案中，所述樣本可以包含在自然界中不與組織自然混合的化合物，例如防腐劑、抗凝劑、緩衝劑、固定劑、營養物、抗生素等。在一些實施方案中，所述樣本包含基因組或亞基因組DNA片段或RNA，例如從樣本（例如腫瘤樣本、正常鄰近組織(NAT)樣本、組織樣本或獲自個體的血液樣本）中單離的mRNA。在一些實施方案中，所述樣本包含源自mRNA樣本或源自包含mRNA的樣本的cDNA。在一些實施方案中，所述樣本包含多肽，例如翻譯後修飾的多肽。在一些實施方案中，所述組織被保藏為冷凍樣本或甲醛或多聚甲醛固定的石蠟包埋(FFPE)組織製品。例如，所述樣本可以嵌入基質中（例如FFPE塊）或為冷凍樣本。A variety of materials (e.g., tissues) can serve as a source of nucleic acid (e.g., DNA or RNA) or polypeptide samples used in the methods provided herein. For example, the source of the sample may be solid tissue from a fresh, frozen and/or preserved organ, tissue sample, biopsy, resection, smear or aspirate; blood or any blood component; body fluids such as cerebrospinal fluid, amniotic fluid, urine fluid, saliva, sputum, peritoneal fluid, or interstitial fluid; or cells at any time during pregnancy or ontogeny. In some embodiments, the sample source is blood or blood components. In some embodiments, the sample source is a tumor sample, such as a colon cancer sample. In some embodiments, the sample is or comprises biological tissue or fluid. In some embodiments, the sample may contain compounds that do not naturally admix with tissue in nature, such as preservatives, anticoagulants, buffers, fixatives, nutrients, antibiotics, and the like. In some embodiments, the sample comprises genomic or subgenomic DNA fragments or RNA, such as mRNA isolated from a sample, such as a tumor sample, a normal adjacent tissue (NAT) sample, a tissue sample, or a blood sample obtained from an individual . In some embodiments, the sample comprises cDNA derived from an mRNA sample or from a sample comprising mRNA. In some embodiments, the sample comprises polypeptides, eg, post-translationally modified polypeptides. In some embodiments, the tissue is preserved as a frozen specimen or as a formaldehyde- or paraformaldehyde-fixed paraffin-embedded (FFPE) tissue preparation. For example, the sample can be embedded in a matrix (eg FFPE block) or be a frozen sample.

在一些實施方案中，所述樣本包含遊離DNA(cfDNA)。在一些實施方案中，所述樣本包含遊離RNA (cfRNA)。在一些實施方案中，所述樣本包含迴圈核酸。在一些實施方案中，所述樣本包含迴圈腫瘤DNA(ctDNA)。In some embodiments, the sample comprises cell-free DNA (cfDNA). In some embodiments, the sample comprises cell-free RNA (cfRNA). In some embodiments, the sample comprises circulating nucleic acid. In some embodiments, the sample comprises circulating tumor DNA (ctDNA).

在一些實施方案中，所述樣本可以是或包含骨髓；骨髓抽出物；血液；血細胞；腹水；組織或穿刺活檢樣本；含有細胞的體液；遊離的漂浮核酸；痰；唾液；尿；腦脊液、腹膜液；胸膜液；糞便；淋巴液；婦科液體；皮膚拭子；陰道拭子；口腔拭子；鼻拭子；沖洗液或灌洗液，例如導管灌洗液或支氣管肺泡灌洗液；吸出物；刮片；骨髓標本；組織活檢標本；手術標本；其他體液、分泌物和/或排泄物；和/或來自其中的細胞。在一些實施方案中，所述生物樣本是或包含從個體獲得的細胞。In some embodiments, the sample can be or comprise bone marrow; bone marrow aspirate; blood; blood cells; ascites; tissue or needle biopsy sample; body fluid containing cells; free floating nucleic acids; fluid; pleural fluid; feces; lymphatic fluid; gynecological fluid; skin swab; vaginal swab; oral swab; nasal swab; douche or lavage fluid, such as catheter lavage or bronchoalveolar lavage; aspirate ; scrapings; bone marrow specimens; tissue biopsy specimens; surgical specimens; other bodily fluids, secretions, and/or excretions; and/or cells derived therefrom. In some embodiments, the biological sample is or comprises cells obtained from an individual.

在一些實施方案中，所述樣本是藉由任何適當方式直接從目的來源獲得的原始樣本。例如，在一些實施方案中，藉由選自活檢(例如針吸活檢或組織活檢)、手術或收集體液(例如血液、淋巴液或糞便)的方法獲得原始生物樣本。在一些實施方案中，如上下文中明確的，術語“樣本”是指藉由處理(例如，藉由去除一種或多種組分和/或藉由向其中添加一種或多種試劑)原始樣本而獲得的製劑。此類處理過的樣本可以包括例如從樣本中提取的或藉由使初級樣本經受諸如擴增或mRNA的逆轉錄、或某些組分的單離和/或純化的技術而獲得的核酸或蛋白質。In some embodiments, the sample is a primary sample obtained directly from the source of interest by any suitable means. For example, in some embodiments, the original biological sample is obtained by a method selected from biopsy (eg, needle biopsy or tissue biopsy), surgery, or collection of bodily fluids (eg, blood, lymph, or feces). In some embodiments, the term "sample" refers to a sample obtained by processing (e.g., by removing one or more components and/or by adding one or more reagents thereto) a raw sample, as clear from the context. preparation. Such processed samples may include, for example, nucleic acids or proteins extracted from the sample or obtained by subjecting the primary sample to techniques such as amplification or reverse transcription of mRNA, or isolation and/or purification of certain components .

在一些實施方案中，所述樣本包含腫瘤核酸，諸如來自腫瘤或癌症樣本的核酸，例如來自腫瘤或癌症樣本的基因組DNA、RNA或源自RNA的cDNA。在某些實施方案中，所述樣本包含腫瘤多肽，例如來自腫瘤或癌症樣本的多肽。在一些實施方案中，所述腫瘤核酸或多肽樣本經過純化或單離(例如將其從其自然狀態中移除)。In some embodiments, the sample comprises tumor nucleic acid, such as nucleic acid from a tumor or cancer sample, eg, genomic DNA, RNA or RNA-derived cDNA from a tumor or cancer sample. In certain embodiments, the sample comprises tumor polypeptides, eg, polypeptides from a tumor or cancer sample. In some embodiments, the tumor nucleic acid or polypeptide sample is purified or isolated (eg, removed from its natural state).

在一些實施方案中，所述樣本是對照核酸樣本或參比核酸樣本，例如基因組DNA、RNA或衍生自RNA的cDNA，其不包含本文所述的異常(例如突變或異常表達/活性/修飾)。在一些實施方案中，所述樣本是對照多肽樣本或參比多肽樣本，不包含本文所述的異常(例如，突變或異常表達/活性/修飾)。在某些實施方案中，所述參比或對照核酸或多肽樣本包含野生型或非突變序列。在某些實施方案中，所述參比核酸或多肽樣本是純化的或單離的(例如其被從其自然狀態中移除)。在其他實施方案中，所述參比核酸或多肽樣本來自非腫瘤樣本，例如血液對照、正常鄰近腫瘤(NAT)或來自相同或不同個體的任何其他非癌性樣本。In some embodiments, the sample is a control nucleic acid sample or a reference nucleic acid sample, such as genomic DNA, RNA, or cDNA derived from RNA, which does not comprise an abnormality (e.g., mutation or aberrant expression/activity/modification) as described herein . In some embodiments, the sample is a control polypeptide sample or a reference polypeptide sample that does not contain an abnormality (eg, mutation or aberrant expression/activity/modification) described herein. In certain embodiments, the reference or control nucleic acid or polypeptide sample comprises wild-type or non-mutated sequences. In certain embodiments, the reference nucleic acid or polypeptide sample is purified or isolated (eg, it has been removed from its natural state). In other embodiments, the reference nucleic acid or polypeptide sample is from a non-tumor sample, such as a blood control, normal adjacent tumor (NAT), or any other non-cancerous sample from the same or a different individual.

系統、軟體和設備Systems, Software and Equipment

在一些其他態樣，本文提供了非暫時性電腦可讀存儲介體。在一些實施方案中，所述非暫時性電腦可讀存儲介體包含用於由設備的一個或多個處理器執行的一個或多個程式，所述一個或多個套裝程式含指令，所述指令在由所述一個或多個處理器執行時使所述設備執行根據本文所述的任一實施方案的方法。In some other aspects, a non-transitory computer-readable storage medium is provided herein. In some embodiments, the non-transitory computer-readable storage medium includes one or more programs for execution by one or more processors of the device, the one or more packaged programs containing instructions, the The instructions, when executed by the one or more processors, cause the apparatus to perform a method according to any of the embodiments described herein.

在一些態樣，本文提供了包含一個或多個處理器和非暫時性電腦可讀存儲介體的系統。In some aspects, provided herein are systems comprising one or more processors and a non-transitory computer-readable storage medium.

在一些實施方案中，本申請的系統包含一個或多個處理器；以及非暫時性電腦可讀存儲介體，其包含一個或多個可由所述一個或多個處理器執行以運行方法的程式。In some embodiments, the system of the present application comprises one or more processors; and a non-transitory computer-readable storage medium comprising one or more programs executable by the one or more processors to perform the method .

在一些實施方案中，所述方法包含以下一項或多項：(a)對一種或多種核酸或多肽進行定序，從而產生多個定序讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析多個定序讀數以確定本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的存在；和(c)基於分析步驟，偵測本申請樣本中的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。In some embodiments, the method comprises one or more of: (a) sequencing one or more nucleic acids or polypeptides, thereby generating a plurality of sequencing reads, wherein the one or more nucleic acids or polypeptides are derived from Samples obtained from individuals with colorectal cancer; (b) analyzing multiple sequenced reads to determine one or more drug sensitivity aberrations (e.g., drug sensitivity mutations) and/or drug resistance aberrations (e.g., drug resistance and (c) based on the assay step, detecting one or more drug sensitivity abnormalities (eg drug sensitivity mutations) and/or drug resistance abnormalities (eg drug resistance mutations) in the sample of the application.

在一些實施方案中，本申請的系統包含被配置為存儲一個或多個程式指令的記憶體；以及被配置為執行所述一個或多個程式指令的一個或多個處理器。In some embodiments, the system of the present application includes memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions.

在一些實施方案中，當所述一杯或多個程式指令由所述一個或多個處理器執行時，其被配置為：(a)獲得一種或多種核酸或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長中是否存在本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)；(c)基於所述分析，偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)。In some embodiments, the one or more programmed instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids or polypeptides, wherein The one or more nucleic acids or polypeptides are derived from samples obtained from individuals with colorectal cancer; (b) analyzing whether there is one or more drug sensitivity abnormalities of the present application in the multiple sequence read lengths (such as drug sensitive mutations) and/or drug resistance abnormalities (such as drug resistance mutations); (c) based on the analysis, detect one or more drug sensitivity abnormalities (such as drug sensitivity mutations) and/or drug resistance abnormalities ( such as resistance mutations).

在一些實施方案中，本申請的系統包含被配置為存儲一個或多個程式指令的記憶體；以及被配置為執行所述一個或多個程式指令的一個或多個處理器。In some embodiments, the system of the present application includes memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions.

在本文提供的任何系統的一些實施方案中，所述一個或多個處理器以及所述包含一個或多個可由一個或多個處理器執行的程式的非暫時性電腦可讀存儲介體位於設備內。在一些實施方案中，所述非暫時性電腦可讀存儲介體包含用於由所述設備的一個或多個處理器執行的一個或多個程式，所述一個或多個程式包括指令，當由一個或多個處理器執行時，所述指令導致所述設備運行根據本文描述的任何實施方案的方法。In some embodiments of any of the systems provided herein, the one or more processors and the non-transitory computer-readable storage medium containing one or more programs executable by the one or more processors are located on a device Inside. In some embodiments, the non-transitory computer-readable storage medium contains one or more programs for execution by the one or more processors of the device, the one or more programs including instructions when When executed by one or more processors, the instructions cause the apparatus to perform a method according to any of the embodiments described herein.

套組set

本文還提供了用於偵測本申請的一種或多種藥物敏感性異常(例如藥物敏感性突變)和/或耐藥異常(例如耐藥突變)的套組。在一些實施方案中，所述套組包含用於偵測藥物敏感性基因和/或耐藥基因的野生型對應物的試劑(例如，本申請的一種或多種寡核苷酸、引子、探針或誘餌)。在一些實施方案中，所述試劑包含本申請的一種或多種寡核苷酸、引子、探針或誘餌，所述寡核苷酸、引子、探針或誘餌能夠與包含本申請的一種或多種藥物敏感性突變和/或耐藥突變(或具有異常表達/活性/修飾)的核酸分子雜交，或與野生型對應物雜交。在一些實施方案中，所述試劑包含本申請的一種或多種誘餌(例如，多肽、抗體或其片段)，所述一種或多種誘餌能夠與由本文所述的一個或多個藥物敏感性基因和/或耐藥基因編碼的一種或多種多肽(例如，野生型，或具有突變或異常表達/活性/修飾)結合。Also provided herein are kits for detecting one or more drug sensitivity abnormalities (eg, drug sensitivity mutations) and/or drug resistance abnormalities (eg, drug resistance mutations) of the present application. In some embodiments, the kit comprises reagents (e.g., one or more oligonucleotides, primers, probes, or bait). In some embodiments, the reagent comprises one or more oligonucleotides, primers, probes or baits of the application, which can be combined with one or more oligonucleotides comprising the application. Nucleic acid molecules with drug-sensitivity mutations and/or drug-resistant mutations (or with aberrant expression/activity/modification) hybridize, or hybridize to wild-type counterparts. In some embodiments, the reagent comprises one or more decoys (e.g., polypeptides, antibodies, or fragments thereof) of the present application that are capable of interacting with one or more drug sensitivity genes and / or one or more polypeptides encoded by drug resistance genes (for example, wild type, or with mutation or abnormal expression/activity/modification) combined.

在一些實施方案中，所述套組用於根據業內已知或本文所述的任何蛋白質或多肽測定，例如質譜法(例如，串聯質譜法)、報告子測定(例如，基於螢光的測定法)、免疫印跡（如蛋白質印跡）、免疫測定（如酶聯免疫吸附測定 (ELISA)）、免疫組織化學、其他免疫測定(例如，液體或凝膠沉澱素反應、免疫擴散、免疫電泳、放射免疫測定(RIA)、免疫螢光測定)和分析生化方法(例如，電泳、毛細管電泳、高效液相層析(HPLC)、薄層層析(TLC)或超擴散層析)。在一些實施方案中，所述套組進一步包含用於偵測由包含本申請的一種或多種改變的基因編碼的多肽（例如，使用本申請的一種或多種抗體）的說明。In some embodiments, the kits are used in accordance with any protein or polypeptide assay known in the art or described herein, such as mass spectrometry (e.g., tandem mass spectrometry), reporter assays (e.g., fluorescence-based assays) ), immunoblotting (eg, Western blot), immunoassay (eg, enzyme-linked immunosorbent assay (ELISA)), immunohistochemistry, other immunoassays (eg, liquid or gel precipitin reaction, immunodiffusion, immunoelectrophoresis, radioimmunoassay Assays (RIA), immunofluorescence assays) and analytical biochemical methods (eg, electrophoresis, capillary electrophoresis, high performance liquid chromatography (HPLC), thin layer chromatography (TLC) or superdiffusion chromatography). In some embodiments, the kit further comprises instructions for detecting a polypeptide encoded by a gene comprising one or more alterations of the present application (eg, using one or more antibodies of the present application).

實施例Example

藉由參考以下實施例將更充分地理解本發明。然而，它們不應被解釋為限制本發明的範疇。應當理解，本文描述的示例和實施例僅用於說明目的，並且再次基礎上的各種修改或變化將向熟習此項技術者給出啟示，其亦將被包括在本申請的精神和範疇內以及所附權利要求的範疇內。The present invention will be more fully understood by reference to the following examples. However, they should not be construed as limiting the scope of the invention. It should be understood that the examples and embodiments described herein are for illustrative purposes only, and that various modifications or changes on this basis will be given to those skilled in the art, and they will also be included within the spirit and scope of the present application and within the scope of the appended claims.

實施例1：癌細胞中藥物敏感性基因和耐藥基因的鑒定Example 1: Identification of Drug Sensitivity Genes and Drug Resistance Genes in Cancer Cells

該實施例提供了用於鑒定DNA損傷劑例如PARPi和ATRi的藥物敏感性基因和/或耐藥基因的示例性方法。簡言之，構建了一個攜帶sgRNA iBAR靶向癌症相關基因的癌細胞庫，用於Cas9介導的基因敲除(KO)。藉由偵測構建的Cas9 +sgRNA iBAR癌細胞庫的抗癌藥物殺傷效果，可以鑒定KO後賦予PARPi或ATRi殺傷耐藥表型或敏感表型的基因。圖1-2顯示了示例性的工作流程。 This example provides exemplary methods for identifying drug susceptibility and/or resistance genes to DNA damaging agents such as PARPi and ATRi. Briefly, a bank of cancer cells carrying sgRNA iBARs targeting cancer-associated genes was constructed for Cas9-mediated gene knockout (KO). By detecting the anticancer drug killing effect of the constructed Cas9 + sgRNA iBAR cancer cell library, the genes that endow PARPi or ATRi killing drug-resistant or sensitive phenotypes after KO can be identified. Figure 1-2 shows an exemplary workflow.

1. sgRNA iBAR文庫的設計與構建 1. Design and construction of sgRNA iBAR library

根據公共資料庫，源自III期和IV期結直腸癌患者的DNA突變頻率≥5%和RNA表達水準上調或下調超過2倍(在細胞內或細胞表面表達)的基因被選為文庫基因，用於進一步的sgRNA iBAR設計(共1323個基因)。 According to public databases, genes with DNA mutation frequency ≥5% and RNA expression levels up-regulated or down-regulated more than 2-fold (expressed in cells or on the cell surface) derived from stage III and stage IV colorectal cancer patients were selected as library genes, For further sgRNA iBAR design (1323 genes in total).

sgRNA iBAR文庫的設計和構建與WO2020125762和Zhu等人(“Guide RNAs with embedded barcodes boost CRISPR-pooled screens,” Genome Biol. 2019; 20:20)中所述類似，每篇文章的內容藉由引用以其整體併入本文。簡言之，上述選擇的1323個基因是從UCSC人類基因組中檢索到的。靶向每個基因的sgRNA是使用DeepRank演算法設計的(參見Zhu等人)，每個基因具有三種不同的靶向sgRNA，並且四個6-bp iBAR(iBAR6s)被隨機分配給每個sgRNA(“sgRNA iBAR”)。內部條碼序列被設計為放置在Cas9-sgRNA核醣核蛋白複合物外部的gRNA支架的四莖環中，不影響其上游引導序列的活性。此外，500個不靶向任何人類基因的對照sgRNA被設計為陰性對照，四個iBAR6s被隨機分配到每個對照sgRNA(“對照sgRNA iBAR”)。因此，設計的CRISPR sgRNA iBAR文庫從而包括共17876個sgRNAsiBAR(目標和對照)。 The design and construction of the sgRNA iBAR library is similar to that described in WO2020125762 and Zhu et al. ("Guide RNAs with embedded barcodes boost CRISPR-pooled screens," Genome Biol. 2019; 20:20), the contents of each article are by reference It is incorporated herein in its entirety. Briefly, the 1323 genes selected above were retrieved from the UCSC human genome. The sgRNAs targeting each gene were designed using the DeepRank algorithm (see Zhu et al.), with three different targeting sgRNAs per gene, and four 6-bp iBARs (iBAR6s) were randomly assigned to each sgRNA ( "sgRNA iBAR "). The internal barcode sequence was designed to be placed in the four-stem loop of the gRNA scaffold outside the Cas9-sgRNA ribonucleoprotein complex without affecting the activity of its upstream guide sequence. In addition, 500 control sgRNAs that did not target any human genes were designed as negative controls, and four iBAR6s were randomly assigned to each control sgRNA (“control sgRNA iBAR ”). Therefore, the designed CRISPR sgRNA iBAR library thus included a total of 17876 sgRNA siBARs (target and control).

設計並合成編碼sgRNAsiBAR的DNA寡核苷酸(由Twist Bioscience)，然後進行PCR擴增。PCR產物用PCR純化套組純化，然後藉由Golden Gate克隆到基於pLenti-sgRNA-Lib(addgene #53121)內部修飾的慢病毒sgRNA iBAR表達骨架中，以獲得sgRNA iBAR質體，該質體編碼15876個sgRNAsiBAR，覆蓋1323個人類基因(每個基因3組sgRNA iBAR，靶向3個不同的靶位點，每組sgRNA iBAR包含4個sgRNA iBAR)，2000個對照sgRNA iBAR靶向500個非基因區域(每個非基因區域有1組sgRNA iBAR，每組sgRNA iBAR包含4個sgRNAsiBAR)。 DNA oligonucleotides (by Twist Bioscience) encoding sgRNAsiBARs were designed and synthesized, followed by PCR amplification. The PCR product was purified with a PCR purification kit, and then cloned by Golden Gate into the lentiviral sgRNA iBAR expression backbone based on the internal modification of pLenti-sgRNA-Lib (addgene #53121) to obtain the sgRNA iBAR plasmid encoding 15876 sgRNA siBARs, covering 1323 human genes (3 groups of sgRNA iBARs for each gene, targeting 3 different target sites, each group of sgRNA iBARs contains 4 sgRNA iBARs ), 2000 control sgRNA iBARs targeting 500 non-gene regions (There is 1 set of sgRNA iBARs per non-genic region, and each set of sgRNA iBARs contains 4 sgRNAsiBARs).

為了確保癌細胞庫中sgRNAsiBAR的豐度(每個sgRNA iBAR至少覆蓋1000倍)，使用上面獲得的sgRNA iBAR質體進行了10次電穿孔反應。對於每次電穿孔反應，將1μL sgRNA iBAR質體添加到1.5mL無菌Eppendorf管中，進一步向管中添加50μL感受態細胞(大腸桿菌)並漩渦，然後進行電穿孔。將不含抗生素的950μL Super Optimal Broth (SOC)培養基立即添加到每個反應管中，用移液器輕輕混合，然後在37°C的搖床上225rpm孵育1小時。將得到的細菌轉移到補充有氨苄青黴素的1L LB液體培養基中，在37°C的搖床上225 rpm培養隔夜。第二天，使用EndoFree® 質體純化套組(QIAGEN, #12391)對獲得的細菌進行質體提取。 To ensure the abundance of sgRNA siBARs in cancer cell banks (at least 1000-fold coverage per sgRNA iBAR ), 10 electroporation reactions were performed using the sgRNA iBAR plastids obtained above. For each electroporation reaction, 1 μL of sgRNA iBAR plasmid was added to a 1.5 mL sterile Eppendorf tube, and 50 μL of competent cells (E. coli) were further added to the tube and vortexed before electroporation. Immediately add 950 μL of Super Optimal Broth (SOC) medium without antibiotics to each reaction tube, mix gently with a pipette, and then incubate on a shaker at 37°C for 1 hour at 225 rpm. The resulting bacteria were transferred to 1 L LB liquid medium supplemented with ampicillin and cultured overnight on a shaker at 225 rpm at 37°C. The next day, plastids were extracted from the obtained bacteria using the EndoFree® Plastid Purification Kit (QIAGEN, #12391).

sgRNA iBAR文庫慢病毒是使用準則方案獲得的。簡言之，將1×107 293T細胞置於150mm細胞培養皿中，加入20mL細胞培養基，然後將293T細胞在37°C、5% CO2培養箱中培養隔夜。次日，棄去培養基，向293T細胞中加入10mL新鮮無血清培養基。使用無血清培養基(4mL)、上述獲得的sgRNA iBAR文庫質體(20μg)、pCMVR8.74質體(20μg)和pCMV-VSV-G質體(2μg)製備轉染複合物；混勻後加入105μL PEI；混合後，將轉染複合物在室溫下靜置15分鐘。然後將轉染複合物添加到10mL新鮮無血清培養基中的293T細胞中，在37°C、5%CO2的培養箱中孵育6小時。棄去細胞培養基。將20 mL新鮮的完全培養基添加到293T細胞中，然後在37°C、5% CO2的培養箱中培養。3天后，收集培養基並在1000rpm、4°C下離心。收集含有sgRNA iBAR文庫慢病毒的上清液，量測病毒滴度，並分裝以備將來使用。 sgRNA iBAR library lentiviruses were obtained using a guideline protocol. Briefly, 1×107 293T cells were placed in a 150 mm cell culture dish, 20 mL of cell culture medium was added, and then the 293T cells were cultured overnight in a 37°C, 5% CO2 incubator. The next day, the medium was discarded, and 10 mL of fresh serum-free medium was added to the 293T cells. Prepare transfection complexes using serum-free medium (4 mL), sgRNA iBAR library plasmids (20 μg) obtained above, pCMVR8.74 plasmids (20 μg) and pCMV-VSV-G plasmids (2 μg); mix well and add 105 μL PEI; After mixing, the transfection complex was allowed to stand for 15 min at room temperature. The transfection complex was then added to 293T cells in 10 mL of fresh serum-free medium and incubated for 6 h in an incubator at 37 °C with 5% CO2. Discard the cell culture medium. Add 20 mL of fresh complete medium to the 293T cells, and then culture them in an incubator at 37°C with 5% CO2. After 3 days, the medium was collected and centrifuged at 1000 rpm, 4°C. Collect the supernatant containing the sgRNA iBAR library lentivirus, measure the virus titer, and aliquot for future use.

2. Cas9 +sgRNA iBAR癌細胞庫的構建 2. Construction of Cas9 + sgRNA iBAR cancer cell bank

選擇HCT116(人結腸癌細胞株)、SW480(人結直腸腺癌細胞株)和Caco2(人結直腸腺癌細胞株)進行Cas9 +sgRNA iBAR癌細胞庫的構建和藥物治療。 HCT116 (human colon cancer cell line), SW480 (human colorectal adenocarcinoma cell line) and Caco2 (human colorectal adenocarcinoma cell line) were selected for construction of Cas9 + sgRNA iBAR cancer cell bank and drug treatment.

將來自每個細胞株的2×105個癌細胞接種在6孔板中，並在37°C、5% CO2培養箱中培養。24小時後，將100μL Cas9包裝的慢病毒加入細胞培養基中，在37°C、5% CO2的培養箱中培養癌細胞。24小時後，棄去培養基，向癌細胞中加入新鮮的完全培養基。讓癌細胞在 37°C、5% CO2的培養箱中生長7天，然後使用mCherry標記(攜帶在Cas9-慢病毒載劑上)藉由FACS分選。分選出的具有mCherry螢光的癌細胞為表達Cas9 (Cas9 +)的細胞，並進行了擴增以構建Cas9 +sgRNA iBAR文庫。 2 × 105 cancer cells from each cell line were seeded in 6-well plates and cultured in a 37°C, 5% CO2 incubator. After 24 hours, 100 μL of Cas9-packaged lentivirus was added to the cell culture medium, and the cancer cells were cultured in an incubator at 37°C and 5% CO2. After 24 hours, the medium was discarded and fresh complete medium was added to the cancer cells. Cancer cells were grown in an incubator at 37°C, 5% CO2 for 7 days, and then sorted by FACS using the mCherry marker (carried on a Cas9-lentiviral vector). Cancer cells with mCherry fluorescence were sorted as Cas9-expressing (Cas9 + ) cells and amplified to construct a Cas9 + sgRNA iBAR library.

為了確保在Cas9 +sgRNA iBAR癌細胞庫中至少1000倍的sgRNA iBAR覆蓋率，將上述獲得的sgRNA iBAR文庫慢病毒以3的感染複數(MOI)添加到培養基(無抗生素)中的2×107 Cas9 +癌細胞中並輕輕混合。Cas9 +癌細胞在37°C、5% CO2培養箱中培養24小時用於感染。第二天，棄去培養基，將新鮮的完全培養基加入到Cas9 +癌細胞中，然後在37°C、5%CO2的培養箱中培養。Cas9 +癌細胞在補充有嘌呤黴素的新鮮完全培養基中每3天傳代一次。沒有成功轉染sgRNA iBAR質體的Cas9 +癌細胞會死亡。連續傳代2-3次後，獲得sgRNA iBAR癌細胞庫(以下分別稱為“Cas9 +sgRNA iBARHCT116庫”、“Cas9 +sgRNA iBARSW480庫”和“Cas9 +sgRNA iBARCaco2庫”)。 To ensure at least 1000-fold sgRNA iBAR coverage in the Cas9 + sgRNA iBAR cancer cell library, the sgRNA iBAR library lentivirus obtained above was added to 2×107 Cas9 in culture medium (without antibiotics) at a multiplicity of infection (MOI) of 3 + cancer cells and mix gently. Cas9 + cancer cells were cultured for 24 h in a 37°C, 5% CO2 incubator for infection. The next day, discard the medium and add fresh complete medium to the Cas9 + cancer cells, then culture in an incubator at 37°C with 5% CO2. Cas9 + cancer cells were passaged every 3 days in fresh complete medium supplemented with puromycin. Cas9 + cancer cells that were not successfully transfected with sgRNA iBAR plastids died. After 2-3 consecutive passages, sgRNA iBAR cancer cell libraries were obtained (hereinafter respectively referred to as "Cas9 + sgRNA iBAR HCT116 library", "Cas9 + sgRNA iBAR SW480 library" and "Cas9 + sgRNA iBAR Caco2 library").

3.篩選抗癌藥物處理的Cas9 +sgRNA iBAR癌細胞庫 3. Screening of Cas9 + sgRNA iBAR cancer cell library treated with anticancer drugs

在用DNA損傷劑(例如，PARP抑制劑(PARPi)或ATR抑制劑(ATRi))處理Cas9 +sgRNA iBAR癌細胞庫之前，量測每個癌細胞株的藥物毒性曲線。 Drug toxicity profiles were measured for each cancer cell line prior to treatment of the Cas9 + sgRNA iBAR cancer cell bank with DNA damaging agents such as PARP inhibitor (PARPi) or ATR inhibitor (ATRi).

將2000 HCT116或SW480或Caco2細胞添加到96孔板中的每個孔中，每個孔添加100μL培養基，然後在37°C、5% CO2細胞培養箱中培養。第二天，將不同濃度的PARPi或ATRi添加到每個孔中，每個濃度3個複孔。PARPi的終濃度為33μM、11μM、3.7μM、1.23μM、0.41μM、0.14μM、0.05μM和0.02μM。ATRi的終濃度為10μM、3.33μM、1.11μM、0.37μM、0.124μM、0.041μM、0.014μM、0.005μM和0.002μM。在PARPi或ATRi存在的情況下，經過三個倍增時長後，進行CellTiter-Glo®發光細胞活性測定(ATP測定)，以獲得藥物毒性曲線。在HCT116和SW480細胞株上測試PARPi。在HCT116和Caco2細胞株上測試ATRi。Add 2000 HCT116 or SW480 or Caco2 cells to each well in a 96-well plate, add 100 μL of medium to each well, and then culture in a 37°C, 5% CO2 cell incubator. The next day, different concentrations of PARPi or ATRi were added to each well, and each concentration was replicated in triplicate. The final concentrations of PARPi were 33 μM, 11 μM, 3.7 μM, 1.23 μM, 0.41 μM, 0.14 μM, 0.05 μM and 0.02 μM. The final concentrations of ATRi were 10 μM, 3.33 μM, 1.11 μM, 0.37 μM, 0.124 μM, 0.041 μM, 0.014 μM, 0.005 μM and 0.002 μM. Drug toxicity curves were obtained by performing the CellTiter-Glo® Luminescent Cell Viability Assay (ATP Assay) after three doubling times in the presence of PARPi or ATRi. PARPi was tested on HCT116 and SW480 cell lines. ATRi was tested on HCT116 and Caco2 cell lines.

根據獲得的每個癌細胞株的藥物毒性曲線，選擇與IC50-IC70的細胞生長抑制相對應的藥物濃度進行Cas9 +sgRNA iBAR癌細胞庫篩選。例如，HCT116和SW480的PARPi濃度分別為5μM和10μM。HCT116的ATRi濃度為0.08μM，Caco2的ATRi濃度為0.1μM。將1×106 Cas9 +sgRNA iBAR癌細胞置於150mm細胞培養皿中，並在37°C、5% CO2細胞培養箱中培養。第二天，用PARPi或ATRi(試驗組)或DMSO(對照組)處理Cas9 +sgRNA iBAR癌細胞。PARPi用Cas9 +sgRNA iBARHCT116文庫和Cas9 +sgRNA iBARSW480文庫上進行測試。ATRi用Cas9 +sgRNA iBARHCT116文庫和Cas9 +sgRNA iBARCaco2文庫上進行測試。每組設兩個生物重複。每三天更換一次新鮮細胞培養基(添加藥物或DMSO)。繼續藥物或對照處理，在處理9-10個倍增時間或15-16個倍增時間後收集細胞(見圖2)。對於貼壁細胞，死細胞會漂浮在培養基中，因此藉由胰蛋白酶處理獲得的貼壁細胞是活的(或大部分是活的)細胞。在整個篩選過程和細胞收集過程中，每個重複的細胞數量始終至少是sgRNA iBAR文庫大小的1000倍，即每個sgRNA iBAR至少有1000個細胞。 According to the drug toxicity curve obtained for each cancer cell line, the drug concentration corresponding to the cell growth inhibition of IC50-IC70 was selected for Cas9 + sgRNA iBAR cancer cell library screening. For example, the PARPi concentrations of HCT116 and SW480 were 5 μM and 10 μM, respectively. The ATRi concentration was 0.08 μM for HCT116 and 0.1 μM for Caco2. 1×106 Cas9 + sgRNA iBAR cancer cells were placed in a 150mm cell culture dish and cultured in a 37°C, 5% CO2 cell incubator. The next day, Cas9 + sgRNA iBAR cancer cells were treated with PARPi or ATRi (test group) or DMSO (control group). PARPi was tested on the Cas9 + sgRNA iBAR HCT116 library and the Cas9 + sgRNA iBAR SW480 library. ATRi was tested on the Cas9 + sgRNA iBAR HCT116 library and the Cas9 + sgRNA iBAR Caco2 library. Two biological replicates were set up for each group. Fresh cell culture medium (addition of drug or DMSO) was changed every three days. Continuing with drug or control treatment, cells were harvested after 9-10 doubling times or 15-16 doubling times of treatment (see Figure 2). For adherent cells, dead cells will float in the medium, so adherent cells obtained by trypsinization are viable (or mostly viable) cells. Throughout the screening process and cell collection, the number of cells per replicate was always at least 1000 times the size of the sgRNA iBAR library, i.e. at least 1000 cells per sgRNA iBAR .

4.靶標基因的鑒定和分析4. Identification and Analysis of Target Genes

從上述收集的處理後的癌細胞(主要是活的Cas9 +sgRNA iBAR癌細胞)中提取基因組DNA。對於每種癌細胞類型，有一個“9-10 PDT試驗組”、一個“15-16PDT試驗小組”、一個“9-10PDT對照組”和一個“15-16PDT對照組”；每組有兩個生物重複。對於PARPi或ATRi，每種抗癌藥物都在兩個不同的細胞株庫中進行了測試。從提取的基因組中PCR擴增sgRNA iBAR編碼片段，純化以備NGS定序。用MAGeCKiBAR演算法進行定序數據分析(見Zhu等人，“Guide RNAs with embedded barcodes boost CRISPR-pooled screens, ” Genome Biol. 2019; 20:20；其內容藉由引用完整納入本文)，其包含三個主要部分：分析準備、統計測試和排序融合。簡單地說，每個sgRNA iBAR靶基因都根據試驗組和對照組之間每個基因的增濃或缺失程度進行評分和排序，以確定該基因是否是一個具有高置信度的候選基因。靶標基因鑒定工作流程見圖3。與對照組(陰性篩選)相比，其失活導致對抗癌藥物殺傷敏感表型的候選基因的sgRNA iBAR編碼片段將耗竭；而與對照(陽性篩選)相比，sgRNA iBAR編碼片段將增濃的候選基因是失活導致對抗癌藥物殺傷的耐藥表型。這些排名靠前的候選者被發現與細胞增殖、細胞死亡、細胞週期調控或免疫反應有關。 Genomic DNA was extracted from the treated cancer cells (mainly live Cas9 + sgRNA iBAR cancer cells) collected above. For each cancer cell type, there is a "9-10 PDT test group", a "15-16PDT test group", a "9-10PDT control group" and a "15-16PDT control group"; each group has two biological repeat. For PARPi or ATRi, each anticancer drug was tested in two different pools of cell lines. The sgRNA iBAR coding fragment was amplified by PCR from the extracted genome and purified for NGS sequencing. Sequencing data analysis was performed using the MAGeCKiBAR algorithm (see Zhu et al., "Guide RNAs with embedded barcodes boost CRISPR-pooled screens," Genome Biol. 2019; 20:20; the contents of which are hereby incorporated by reference in their entirety), comprising three There are three main sections: analysis preparation, statistical testing, and sequencing fusion. Briefly, each sgRNA iBAR target gene was scored and ranked according to the degree of enrichment or deletion of each gene between test and control groups to determine whether the gene is a candidate gene with high confidence. The target gene identification workflow is shown in Figure 3. sgRNA iBAR coding fragments of candidate genes whose inactivation leads to anticancer drug killing-sensitive phenotypes will be depleted compared to controls (negative screening), whereas sgRNA iBAR coding fragments will be enriched compared to controls (positive screening) Candidate genes for inactivation lead to a drug-resistant phenotype of anticancer drug killing. These top-ranked candidates were found to be related to cell proliferation, cell death, cell cycle regulation, or immune response.

5.結果5. Results

與對照組相比，其sgRNA iBAR編碼片段在“9-10 PDT試驗組”或“15-16 PDT試驗組”以及FDR≤0.1的任一細胞株庫(例如，用於PARPi的Cas9 +sgRNA iBARHCT116庫或Cas9 +sgRNA iBARSW480庫)中收集的活細胞中耗竭的候選基因被歸類為藥物敏感性基因，其失活使癌細胞對抗癌藥物敏感。PARPi的典型藥物敏感性基因如表3、A、9和10所示。ATRi的典型藥物敏感性基因如表4所示。 Compared with the control group, its sgRNA iBAR coding fragment was in the "9-10 PDT test group" or "15-16 PDT test group" and any cell line library with FDR≤0.1 (for example, Cas9 + sgRNA iBAR for PARPi Candidate genes depleted in live cells collected in the HCT116 library or the Cas9 + sgRNA iBAR SW480 library) were classified as drug-sensitive genes whose inactivation sensitizes cancer cells to anticancer drugs. Typical drug susceptibility genes of PARPi are shown in Tables 3, A, 9 and 10. The typical drug sensitivity genes of ATRi are shown in Table 4.

與對照組相比，其sgRNA iBAR編碼片段在“9-10 PDT試驗組”或“15-16 PDT試驗組”以及在FDR≤0.1的任一細胞株庫中收集的活細胞中增濃的候選基因被歸類為耐藥基因，其失活使癌細胞對抗癌藥物產生耐藥性。PARPi的典型耐藥基因如表7、B、9和10所示。ATRi的典型耐藥基因如表8所示。 Candidates whose sgRNA iBAR coding fragments were enriched in "9-10 PDT test group" or "15-16 PDT test group" and in live cells collected in any cell line bank with FDR ≤ 0.1 compared to controls Genes are classified as drug resistance genes, the inactivation of which renders cancer cells resistant to anticancer drugs. Typical resistance genes of PARPi are shown in Tables 7, B, 9 and 10. Typical drug resistance genes of ATRi are shown in Table 8.

表9顯示了用篩選分數(反映增濃/耗竭的顯著性和程度)和FDRs(反映顯著性)在PARPi的Cas9 +sgRNA iBARHCT116庫或Cas9 +sgRNA iBARSW480庫的“15-16 PDT試驗組”中確定的PARPi敏感和耐藥基因子集。 Table 9 shows the "15-16 PDT test groups" using screening scores (reflecting the significance and degree of enrichment/depletion) and FDRs (reflecting significance) in PARPi's Cas9 + sgRNA iBAR HCT116 library or Cas9 + sgRNA iBAR SW480 library A subset of PARPi sensitive and resistant genes identified in ".

表9. PARPi的藥物敏感性或耐藥基因 PARPI的藥物敏感性基因 PARPI的耐藥基因 基因 篩選分數 FDR 基因 篩選分數 FDR  PTEN 27.72 0.00 PARP1 34.15 0.00 ATM 26.01 0.00 MED12 33.39 0.00  RIF1 24.53 0.00  MAPK1 30.19 0.00 BRCA1 23.82 0.00 TCF7L2 27.27 0.00  TSC1 20.37 0.00  CKS2 20.86 0.00 STAG1 19.29 0.00  TP53 20.70 0.00  FBXW7 19.25 0.00  HSP90B1 20.20 0.00 NBN 19.23 0.00  CDKN1A 20.17 0.00  CHD7 16.84 0.00 TP53BP1 18.56 0.00  SKP2 16.56 0.00 RHEB 18.34 0.00  GSK3B 15.55 0.00 CTNNB1 18.09 0.00  TSC2 14.79 0.00 ILK 17.88 0.00  POLQ 13.56 0.00 MYC 17.75 0.00  CDK2 11.13 0.00 PARP2 17.62 0.00  FANCM 9.87 0.00 RICTOR 17.47 0.00 ATR 8.98 0.00 ZMYND8 17.46 0.00 SCAF4 7.55 0.00 PIK3CA 14.84 0.00 BIRC6 7.48 0.00  RAC1 14.76 0.00  PBRM1 7.31 0.00 RAPGEF1 14.22 0.00  KAT2B 7.12 0.00 GCN1 13.96 0.00  GSK3A 7.07 0.00 EIF3A 13.11 0.00  NIPBL 6.90 0.00 SMAD4 12.46 0.00  HRAS 6.80 0.00  DLG5 11.37 0.00  TGFB2 6.78 0.00 CHD2 11.23 0.00 WEE1 6.66 0.00 BRAF 10.87 0.00  CCNA2 6.20 0.00  AKT1 10.76 0.00 HDAC2 5.91 0.00 IGF1R 10.50 0.00  AXIN1 5.72 0.00  CKS1B 10.07 0.00  SMAD7 4.77 0.01 IRS1 9.38 0.00 ARID2 4.10 0.03  RBL1 8.59 0.00  CCND1 3.52 0.09 DOCK5 7.75 0.00 DIDO1 3.42 0.08 KMT2B 6.56 0.00 BRCA2 3.36 0.11 EP300 5.90 0.00          SETD2 5.15 0.00          PKMYT1 5.08 0.00           CCNA1 4.72 0.01           E2F3 4.68 0.01          SPTA1 4.57 0.02           HDAC1 4.18 0.02           E2F4 3.43 0.15 Table 9. Drug sensitivity or resistance genes of PARPi PARPI Drug Sensitivity Genes PARPI resistance gene Gene screening score FDR Gene screening score FDR PTEN 27.72 0.00 PARP1 34.15 0.00 ATMs 26.01 0.00 MED12 33.39 0.00 RIF1 24.53 0.00 MAPK1 30.19 0.00 BRCA1 23.82 0.00 TCF7L2 27.27 0.00 TSC1 20.37 0.00 CKS2 20.86 0.00 STAG1 19.29 0.00 TP53 20.70 0.00 FBXW7 19.25 0.00 HSP90B1 20.20 0.00 NBN 19.23 0.00 CDKN1A 20.17 0.00 CHD7 16.84 0.00 TP53BP1 18.56 0.00 SKP2 16.56 0.00 RHEB 18.34 0.00 GSK3B 15.55 0.00 CTNNB1 18.09 0.00 TSC2 14.79 0.00 ILK 17.88 0.00 POLQ 13.56 0.00 MYC 17.75 0.00 CDK2 11.13 0.00 PARP2 17.62 0.00 FANCM 9.87 0.00 RICTOR 17.47 0.00 ATR 8.98 0.00 ZMYND8 17.46 0.00 SCAF4 7.55 0.00 PIK3CA 14.84 0.00 BIRC6 7.48 0.00 RAC1 14.76 0.00 PBRM1 7.31 0.00 RAPGEF1 14.22 0.00 KAT2B 7.12 0.00 GCN1 13.96 0.00 GSK3A 7.07 0.00 EIF3A 13.11 0.00 NIPBL 6.90 0.00 SMAD4 12.46 0.00 HRAS 6.80 0.00 DLG5 11.37 0.00 TGFB2 6.78 0.00 CHD2 11.23 0.00 WEE1 6.66 0.00 BRAF 10.87 0.00 CCNA2 6.20 0.00 AKT1 10.76 0.00 HDAC2 5.91 0.00 IGF1R 10.50 0.00 AXIN1 5.72 0.00 CKS1B 10.07 0.00 SMAD7 4.77 0.01 IRS1 9.38 0.00 ARID2 4.10 0.03 RBL1 8.59 0.00 CCND1 3.52 0.09 DOCK5 7.75 0.00 DIDO1 3.42 0.08 KMT2B 6.56 0.00 BRCA2 3.36 0.11 EP300 5.90 0.00 SETD2 5.15 0.00 PKMYT1 5.08 0.00 CCNA1 4.72 0.01 E2F3 4.68 0.01 SPTA1 4.57 0.02 HDAC1 4.18 0.02 E2F4 3.43 0.15

此處獲得的結果，特別是那些其失活被發現可以使癌細胞對抗癌藥物(如PARPi或ATRi)殺傷敏感的基因，論證了癌症治療中的有價值的標靶以及用於患者選擇的生物標記物。其失活使癌細胞對抗癌藥物產生耐藥性的耐藥基因將作為不選擇此類患者和/或應使用替代癌症治療劑的生物標記物。The results obtained here, particularly those genes whose inactivation was found to sensitize cancer cells to killing by anticancer drugs such as PARPi or ATRi, demonstrate valuable targets in cancer therapy and potential candidates for patient selection. biomarkers. Resistance genes whose inactivation renders cancer cells resistant to anticancer drugs would serve as biomarkers for not selecting such patients and/or for alternative cancer therapeutics.

6.靶基因的驗證6. Validation of target genes

為了驗證已識別的藥物敏感性基因和耐藥基因，從PARPi敏感基因和PARPi耐藥基因(見表10)中選擇基因子集進行實驗測試。In order to verify the identified drug sensitivity genes and drug resistance genes, a gene subset was selected from PARPi sensitive genes and PARPi drug resistant genes (see Table 10) for experimental testing.

簡言之，設計並合成了編碼靶向這些基因的sgRNA的核酸。允許正鏈和反鏈退火，以形成兩端懸垂的雙鏈核酸。酶切基於pLenti-sgRNA-Lib (addgene #53121)自行修飾獲得的慢病毒sgRNA iBAR表達骨架，將雙鏈核酸連接到切割位點以獲得sgRNA質體。該sgRNA質體攜帶嘌呤黴素和氨苄西林抗生素基因。 Briefly, nucleic acids encoding sgRNAs targeting these genes were designed and synthesized. The forward and reverse strands are allowed to anneal to form a double-stranded nucleic acid with overhangs at both ends. Enzyme digestion is based on the lentiviral sgRNA iBAR expression backbone modified by pLenti-sgRNA-Lib (addgene #53121), and the double-stranded nucleic acid is connected to the cutting site to obtain the sgRNA plasmid. The sgRNA plasmid carries the puromycin and ampicillin antibiotic genes.

為了擴增sgRNA質體，將2μL sgRNA質體添加到位於1.5 mL Eppendorf管中的20μL感受態細胞(大腸桿菌)中，然後按照準則的冰/熱激轉化方案，讓其在37°C搖床中的液體LB中生長1小時，然後塗布到LBAmp +板上並在37℃生長隔夜。第二天，挑選5-10個單克隆，讓其在37°C搖床中的液體LBAmp +培養基中隔夜生長。第二天，用套組提取sgRNA質體，然後定序以驗證序列。 To amplify sgRNA plasmids, add 2 μL of sgRNA plasmids to 20 μL of competent cells (E. coli) in a 1.5 mL Eppendorf tube, then follow the guideline ice/heat shock transformation protocol and let shake at 37°C. Grow in liquid LB for 1 hr, then spread onto LBAmp + plates and grow overnight at 37 °C. The next day, pick 5-10 single colonies and let them grow overnight in liquid LBAmp + medium in a shaker at 37°C. The next day, kits were used to extract sgRNA plasmids and then sequenced to verify the sequence.

然後使用準則方案獲得sgRNA慢病毒。簡言之，將5×106 293T細胞置於10cm細胞培養皿中，並在37°C、5% CO2培養箱中培養隔夜。第二天，棄去培養基，向293T細胞中添加新鮮無血清培養基。用無血清培養基(1mL)、上述純化的sgRNA質體(10μg)、pCMVR8.74質體(10微克)和pCMV-VSV-G質體(1微克)製備轉染複合物；混合後，添加52.5μL PEI。混合後，將轉染複合物在室溫靜置15分鐘。然後將轉染複合物添加到在新鮮無血清培養基中的293T細胞，在37°C、5% CO2培養箱中培養6-8小時。棄去細胞培養基，將新鮮的完全培養基添加到293T細胞中，然後在37°C、5% CO2培養箱中培養。72小時後，收集細胞培養物並在200g離心5分鐘。收集含有sgRNA慢病毒的上清液，用0.45μm篩檢程式過濾，然後儲存在-80°C供將來使用。sgRNA lentiviruses were then obtained using the guideline protocol. Briefly, 5×106 293T cells were placed in a 10 cm cell culture dish and cultured overnight in a 37°C, 5% CO2 incubator. The next day, the medium was discarded and fresh serum-free medium was added to the 293T cells. Prepare transfection complexes with serum-free medium (1 mL), the above purified sgRNA plasmids (10 μg), pCMVR8.74 plasmids (10 μg) and pCMV-VSV-G plasmids (1 μg); after mixing, add 52.5 μL PEI. After mixing, the transfection complex was allowed to stand at room temperature for 15 minutes. The transfection complex was then added to 293T cells in fresh serum-free medium and incubated in a 37°C, 5% CO2 incubator for 6-8 hours. Discard the cell culture medium, add fresh complete medium to the 293T cells, and culture them in a 37°C, 5% CO2 incubator. After 72 hours, cell cultures were harvested and centrifuged at 200g for 5 minutes. The supernatant containing the sgRNA lentivirus was collected, filtered with a 0.45 μm screening program, and then stored at -80 °C for future use.

為了構建具有靶基因KO的癌細胞株，將2×105 SW620癌細胞接種在6孔板中，並在37°C、5% CO2培養箱中培養。24小時後，向細胞培養基中添加100μL Cas9包裝慢病毒，並在37°C、5% CO2培養箱中培養癌細胞。24小時後，棄去培養基，將新鮮的完全培養基添加到癌細胞中。讓癌細胞在37°C、5% CO2培養箱中生長7天，然後用mCherry標記(Cas9慢病毒載劑攜帶的)藉由FACS進行分選。篩選出的具有mCherry螢光的癌細胞為表達Cas9(Cas9 +)的細胞，並進行擴增以構建Cas9 +sgRNA。將上述獲得的500μL非濃縮sgRNA慢病毒以3的感染複數(MOI)添加到培養基(無抗生素)中的2×107 Cas9 +癌細胞中，並輕輕混合。Cas9 +癌細胞在37°C、5% CO2培養箱中培養隔夜以進行感染。第二天，棄去培養基，將新鮮的完全培養基添加到Cas9 +癌細胞中，然後在37°C、5% CO2培養箱中培養48小時。然後向培養基中添加1μL嘌呤黴素進行篩選。未成功轉染sgRNA質體的Cas9 +癌細胞會死亡。 To construct cancer cell lines with target gene KO, 2×105 SW620 cancer cells were seeded in 6-well plates and cultured in a 37°C, 5% CO2 incubator. After 24 h, add 100 μL of Cas9-packaged lentivirus to the cell culture medium and culture the cancer cells in a 37°C, 5% CO2 incubator. After 24 hours, the medium was discarded and fresh complete medium was added to the cancer cells. The cancer cells were grown in a 37°C, 5% CO2 incubator for 7 days, and then sorted by FACS with the mCherry marker (carried by the Cas9 lentiviral vector). The selected cancer cells with mCherry fluorescence are cells expressing Cas9 (Cas9 + ), and amplified to construct Cas9 + sgRNA. Add 500 μL of the non-condensed sgRNA lentivirus obtained above to 2×107 Cas9 + cancer cells in medium (without antibiotics) at a multiplicity of infection (MOI) of 3 and mix gently. Cas9 + cancer cells were cultured overnight in a 37°C, 5% CO2 incubator for infection. The next day, the medium was discarded, and fresh complete medium was added to the Cas9 + cancer cells, followed by culturing in a 37°C, 5% CO2 incubator for 48 hours. Then add 1 μL of puromycin to the medium for selection. Cas9 + cancer cells unsuccessfully transfected with sgRNA plastids die.

為了測試靶基因KO的效率(%)，收集上述嘌呤黴素處理的癌細胞亞群。提取基因組DNA，擴增靶標基因序列並定序。KO效率是藉由分解跟蹤插入缺失(TIDE)網路工具計算的，該工具可以從序列跟蹤中準確地重建插入缺失的頻譜，並將偵測到的插入缺失及其頻率報告為KO效率。結果匯總於表10。To test the efficiency (%) of target gene KO, the above puromycin-treated cancer cell subpopulations were collected. Genomic DNA is extracted, the target gene sequence is amplified and sequenced. KO efficiencies were calculated with the Decomposition Tracking Indels (TIDE) web tool, which accurately reconstructs indel spectra from sequence traces and reports detected indels and their frequencies as KO efficiencies. The results are summarized in Table 10.

為了測試靶基因KO癌細胞對PARPi處理的反應，將每個靶基因KO的1000個癌細胞放入96孔板中，每孔都添加培養基，然後在37°C、5% CO2細胞培養箱中培養隔夜。第二天，以1:3的稀釋度製備不同濃度的PARPi，然後添加到每個孔中，每個濃度3個重複。PARPi的終濃度為33.3μM、11.1μM、3.70μM、1.27μM、0.41μM、0.13μM，0.05μM和0.015μM。用不攜帶任何靶基因KO(“WT癌細胞”)的癌細胞，在相同條件下培養並用PARPi處理，進行了一組對照實驗。在PARPi存在的情況下經過2-3個倍增時間後，進行CellTiter Glo®發光細胞活性測定(ATP測定)，以獲得藥物毒性曲線(見圖4)。IC50結果如表10所示。In order to test the response of target gene KO cancer cells to PARPi treatment, 1000 cancer cells KO of each target gene were placed in a 96-well plate, medium was added to each well, and then incubated in a 37°C, 5% CO2 cell incubator. Incubate overnight. The next day, different concentrations of PARPi were prepared at a 1:3 dilution and added to each well in triplicate for each concentration. The final concentrations of PARPi were 33.3 μM, 11.1 μM, 3.70 μM, 1.27 μM, 0.41 μM, 0.13 μM, 0.05 μM and 0.015 μM. A set of control experiments were performed using cancer cells not carrying any target gene KO ("WT cancer cells"), cultured under the same conditions and treated with PARPi. After 2-3 doubling times in the presence of PARPi, the CellTiter Glo® Luminescent Cell Viability Assay (ATP Assay) was performed to obtain drug toxicity curves (see Figure 4). IC50 results are shown in Table 10.

表10. PARPi的藥物敏感性基因和耐藥基因的驗證 PARPI的藥物敏感性基因 PARPI的耐藥基因 基因 KO 效率 (%) IC50 倍數變化(KO VS. WT) 基因 KO 效率 (%) IC50 倍數變化 (KO VS. WT) ATM 80 -56.45 MYC 57 6.43 NBN 51 -15.96 GCN1 62 5.50 FANCM 69 -13.27 ZMYND8 40 5.50 BRCA1 90 -9.86 PARP1 75 3.48 WEE1 63 -8.69 SETD2 57 2.50 ARID2 87 -5.55 RICTOR 60 2.42  RIF1 68 -3.55 CTNNB1 47 2.00  CHD7 76 -3.06  TP53 79 1.94  POLQ 58 -1.88 EIF3A 29 1.77 DIDO1 58 -1.88 MED12 70 1.50  PTEN 51 -1.78          ATR 32 -1.67          STAG1 70 -1.63          BIRC6 88 -1.50          Table 10. Validation of drug susceptibility genes and drug resistance genes of PARPi PARPI Drug Sensitivity Genes PARPI resistance gene Gene KO efficiency (%) IC50 Fold Change (KO VS. WT) Gene KO efficiency (%) IC50 Fold Change (KO VS. WT) ATMs 80 -56.45 MYC 57 6.43 NBN 51 -15.96 GCN1 62 5.50 FANCM 69 -13.27 ZMYND8 40 5.50 BRCA1 90 -9.86 PARP1 75 3.48 WEE1 63 -8.69 SETD2 57 2.50 ARID2 87 -5.55 RICTOR 60 2.42 RIF1 68 -3.55 CTNNB1 47 2.00 CHD7 76 -3.06 TP53 79 1.94 POLQ 58 -1.88 EIF3A 29 1.77 DIDO1 58 -1.88 MED12 70 1.50 PTEN 51 -1.78 ATR 32 -1.67 STAG1 70 -1.63 BIRC6 88 -1.50

如圖4和表10所示，KO後篩選出的藥物敏感性基因確實賦予了癌細胞對PARPi殺傷的敏感性(例如，見ATM、BRCA1、WEE1等)，而KO後篩查出的耐藥基因賦予了癌細胞對PARPi殺傷的抗性(例如，見PARP1、MYC)。此外，靶基因KO和WT癌細胞之間的IC50倍數變化在很大程度上遵循篩選結果：篩選出的高度增濃或耗竭的靶基因(例如，較高的篩選分數，例如見表9)也在IC50上顯示了較大的差異。As shown in Figure 4 and Table 10, the drug-sensitive genes screened after KO did endow cancer cells with susceptibility to PARPi killing (for example, see ATM, BRCA1, WEE1, etc.), while the drug-resistant genes screened after KO Genes that confer resistance to cancer cell killing by PARPi (eg, see PARP1, MYC). Furthermore, the IC50 fold change between KO and WT cancer cells for target genes largely followed the screening results: highly enriched or depleted target genes (e.g., higher screening scores, e.g., see Table 9) were also screened out. Larger differences were shown on IC50.

這些靶基因驗證結果表明，本文描述的篩選方法在獲得藥物敏感性基因和/或耐藥基因態樣是有效的，並且本文提供的藥物敏感性基因或耐藥基因具有高準確度，在癌症診斷和治療中具有重要價值。These target gene verification results show that the screening method described herein is effective in obtaining drug-sensitive genes and/or drug-resistant gene patterns, and the drug-sensitive genes or drug-resistant genes provided herein have high accuracy and are useful in cancer diagnosis. It is of great value in and treatment.

7.討論7. Discussion

上述方法可用於任何抗癌藥物(例如針對不同通路或相同通路的藥物)和任何癌症類型的藥物敏感性基因和/或耐藥基因的篩查。獲得的藥物敏感性基因和/或耐藥基因在癌症治療、患者選擇和新藥篩選或設計中具有重要意義。The method described above can be used for screening of any anticancer drugs (such as drugs targeting different pathways or the same pathway) and drug sensitivity genes and/or drug resistance genes of any cancer type. The obtained drug sensitivity genes and/or drug resistance genes are of great significance in cancer treatment, patient selection and new drug screening or design.

例如，如果癌症患者的診斷表明，對於單一通路(例如PARPi靶向等)：1)患者在靶基因中只有導致對通路靶向藥物敏感的失活突變，則該患者是使用此類藥物治療的完美候選者；2) 患者在靶基因中只有導致對通路靶向藥物產生抗性的失活突變，則該患者可能不適合使用靶向該通路的藥物進行治療，應尋求替代治療方法；3) 患者在兩種靶基因(其失活導致對通路靶向藥物的抗性的靶基因和其失活導致對通路靶向藥物敏感的靶基因)中都有失活突變，則需要進行更多分析，例如：在出現耐藥之前藥物敏感性是否足以幫助殺死癌細胞；與賦予藥物敏感性的基因相比，賦予耐藥性的基因在癌症發展中是否重要性更小；是否應選擇一種通路靶向藥物而不選擇另一種通路靶向藥物；一種藥物是否應先於另一種藥物使用或一起使用；是否存在替代治療方法等。本文描述的藥物敏感性異常和耐藥異常的綜合評分(例如公式I)也可有助於治療決策。For example, if the diagnosis of a cancer patient shows that, for a single pathway (e.g., PARPi targeting, etc.): 1) the patient has only inactivating mutations in the target gene that result in sensitivity to a pathway-targeting drug, then the patient is treated with such drug perfect candidate; 2) the patient has only an inactivating mutation in the target gene that confers resistance to pathway-targeted drugs, then the patient may not be suitable for treatment with drugs targeting the pathway and alternative treatments should be sought; 3) the patient In the presence of inactivating mutations in both target genes (the target gene whose inactivation results in resistance to pathway-targeted drugs and the target gene whose inactivation results in sensitivity to pathway-targeted drugs), more analysis is required, For example: whether drug sensitivity is sufficient to help kill cancer cells before resistance emerges; whether genes that confer drug resistance are less important in cancer development than genes that confer drug sensitivity; whether a pathway target should be chosen Towards a drug rather than another pathway-targeted drug; whether one drug should be used before or together with another; whether alternative treatments exist, etc. A composite score of drug susceptibility abnormalities and drug resistance abnormalities described herein (eg, Formula I) can also aid in treatment decisions.

針對多個抗癌藥物獲得的靶基因，例如靶向與癌症發展相關的相同或不同通路的抗癌藥物(例如PARPi和ATRi，兩者都與DNA損傷有關，但靶向不同通路)，可以組合或重迭以找到共同的靶基因。可以進一步分析基因功能和/或作用機制，以作出治療決策和/或藥物設計/開發。例如，如果患者攜帶的基因發生失活突變，其失活導致對藥物X、Y和Z敏感，那麼與藥物X、Y和Z的聯合治療可能會產生協同抗癌活性。例如，如果患者攜帶不同基因(相同或不同通路)的失活突變，所述基因的失活導致對藥物X、Y和Z敏感，那麼使用藥物X、Y和Z的聯合治療可能會產生協同抗癌活性。另一個例子是，如果一種新藥可以被設計成靶向涉及靶基因的各種通路，而所述靶基因的缺失會導致對已知藥物的敏感性，則與已知藥物相比，獲得的新藥可能具有更好的治療效果。Target genes obtained for multiple anticancer drugs, such as anticancer drugs targeting the same or different pathways involved in cancer development (such as PARPi and ATRi, both related to DNA damage but targeting different pathways), can be combined or overlap to find common target genes. Gene function and/or mechanism of action can be further analyzed for therapeutic decision and/or drug design/development. For example, if a patient carries an inactivating mutation in a gene whose inactivation confers sensitivity to drugs X, Y, and Z, combination therapy with drugs X, Y, and Z may result in synergistic anticancer activity. For example, if a patient carries inactivating mutations in different genes (same or different pathways) whose inactivation results in sensitivity to drugs X, Y, and Z, combination therapy with drugs X, Y, and Z may result in synergistic resistance. cancer activity. As another example, if a new drug could be designed to target various pathways involving target genes whose loss would result in sensitivity to a known drug, the resulting new drug might be less likely than the known drug. have a better therapeutic effect.

例如，對於PARPi、ATRi、其他治療結直腸癌的藥物、或其他治療其他癌症類型但尚未測試/開發用於結直腸癌治療的藥物等所靶向的各種通路，如果患者被診斷為患者1)在共有靶基因(或共有通路的不同基因)中有失活突變，其失活導致對各種通路靶向藥物敏感，則可以使用單一或最好與這些藥物聯合治療癌症; 2)在共有靶基因(或具有共有通路的不同基因)中發生失活突變，其失活導致對各種通路靶向藥物產生耐藥性，則應尋求替代治療方法，或者應該進一步分析基因功能和/或作用機制，以確定使用這種通路靶向藥物的聯合治療(例如，一種先於另一種使用)是否可以緩解耐藥表型。例如，可以首先使用在治療過程中稍後因靶標基因突變而產生耐藥性的藥物X，在治療過程中，由於靶基因突變而對其產生耐藥性的藥物X可以首先使用；而在早期因靶基因突變而對其產生耐藥性但可能足夠有效的藥物Y，只能在最初或整個過程中與藥物X結合使用。For example, for various pathways targeted by PARPi, ATRi, other drugs for colorectal cancer, or other drugs that treat other cancer types but have not been tested/developed for colorectal cancer treatment, etc., if the patient is diagnosed as Patient 1) There are inactivating mutations in shared target genes (or different genes of shared pathways), whose inactivation leads to sensitivity to various pathway-targeted drugs, and cancer can be treated with single or preferably in combination with these drugs; 2) in shared target genes Inactivating mutations in (or different genes with shared pathways) that confer resistance to various pathway-targeted drugs should seek alternative therapeutic approaches, or further analysis of gene function and/or mechanism of action should be performed to To determine whether combination therapy (e.g., one administered before the other) with such pathway-targeting agents can alleviate the drug-resistant phenotype. For example, drug X that develops resistance due to target gene mutations later in the course of treatment can be used first; Drug Y, which is resistant to it due to mutations in the target gene, but may be effective enough, can only be combined with drug X initially or throughout the course.

實施例2：綜合評分正確反映抗癌藥物的抗癌療效Example 2: The comprehensive score correctly reflects the anticancer efficacy of anticancer drugs

本實施例提供了證據，證明採用本文所述篩選方法確定的基於抗癌劑(例如PARPi或ATRi等DNA損傷劑)的藥物敏感性基因和耐藥基因的根據本文所述方法(如公式I)計算的綜合評分，能正確反映/預測相應抗癌劑的抗癌效果。This example provides evidence that the drug susceptibility genes and drug resistance genes based on anticancer agents (such as DNA damaging agents such as PARPi or ATRi) determined by the screening methods described herein are determined according to the methods described herein (such as formula I) The calculated comprehensive score can correctly reflect/predict the anticancer effect of the corresponding anticancer agent.

1.隨機選取結直腸癌樣本計算綜合評分1. Randomly select colorectal cancer samples to calculate the comprehensive score

藉由採用準則方法量測細胞存活率(反映為IC50)或PDX生長抑制率，測試了收集的結直腸癌細胞株和患者來源的異種移植物(PDX)對PARPi治療的應答(也見實施例1)。基於對PARPi治療的不同應答，選擇16個癌症樣本(10個PDX和6個癌細胞株；參見圖5A)，用於計算綜合評分。其相應的細胞活性應答或PDX生長抑制應答在圖5C中反映為“藥物應答”。Harvested colorectal cancer cell lines and patient-derived xenografts (PDX) were tested for response to PARPi treatment by measuring cell viability (reflected as IC50) or PDX growth inhibition using standard methods (see also Example 1). Based on the different responses to PARPi treatment, 16 cancer samples (10 PDX and 6 cancer cell lines; see Figure 5A) were selected for the calculation of the composite score. Its corresponding cellular viability response or PDX growth inhibitory response is reflected as "drug response" in Figure 5C.

2.偵測、篩選和標注選定癌症樣本中的突變2. Detection, screening and labeling of mutations in selected cancer samples

以上選定的16個癌症樣本藉由NGS單獨定序。對於每個樣本，從定序數據中偵測突變。根據突變品質進一步篩選原始突變位點，以去除低置信度的突變位點。剩餘的高品質突變位點被映射到相應的基因，並基於資料庫標注所述突變對相應基因功能的影響。只有對相應基因有有害影響的突變位點被保留下來進行後續分析。The 16 cancer samples selected above were individually sequenced by NGS. For each sample, mutations were detected from the sequencing data. The original mutation sites were further screened according to the mutation quality to remove low confidence mutation sites. The remaining high-quality mutation sites were mapped to the corresponding genes, and the effects of the mutations on the corresponding gene functions were annotated based on the database. Only mutation sites with deleterious effects on the corresponding genes were retained for subsequent analysis.

3.基因級別的功能標注和一系列資料庫資訊集成以進一步篩選3. Gene-level functional annotation and a series of database information integration for further screening

然後，根據來自外部和內部資料庫來源的患病率、臨床重要性、策劃影響、基因本體論和通路資訊等，對上述其餘突變位點進行標注。進一步篩選出低臨床影響突變。然後計算每個樣本中映射到剩餘突變的每個基因的總體功能喪失(LOF)概率。The remaining mutation sites above were then annotated based on prevalence, clinical importance, curated impact, Gene Ontology, and pathway information from external and internal database sources. Mutations with low clinical impact were further screened out. The overall loss-of-function (LOF) probability for each gene mapped to the remaining mutations in each sample was then calculated.

4.綜合評分計算4. Comprehensive score calculation

為了計算每個癌症樣本的綜合評分並測試其預測PARPi治療反應的準確性，總共選擇了51個PARPi敏感基因和PARPi耐藥基因，這些基因是從實施例1中獲得和/或在實施例1中驗證的，並且在篩選後的16個所選癌症樣本中的任何一個樣本中至少有一個高置信度的有害突變(“測試基因小組”)。其相應的LOF概率如圖5A所示。對於每個癌症樣本，使用51個PARPi敏感/耐藥基因基因水準的LOF概率計算公式I中的

Figure 02_image066
部分。藉由整合相應的權重(
Figure 02_image021
)、每個基因的相關係數(
Figure 02_image018
)、和PARPi反應中相關通路的預計算權重(
Figure 02_image071
)來量化“測試基因小組”中偵測到的突變對PARPi治療的基因水準貢獻和通路水準貢獻，以計算原始綜合評分。根據樣本類型(即細胞株、PDX、患者)進一步調整和按比例調節原始綜合評分，以生成每個癌症樣本的最終綜合評分(見圖5B和5C“綜合評分”行)。 In order to calculate a composite score for each cancer sample and test its accuracy in predicting response to PARPi therapy, a total of 51 PARPi-sensitive genes and PARPi-resistant genes were selected, which were obtained from Example 1 and/or described in Example 1 Validated in and with at least one deleterious mutation with high confidence in any of the 16 selected cancer samples after screening ("Test Genome Panel"). Its corresponding LOF probability is shown in Fig. 5A. For each cancer sample, use the LOF probability of 51 PARPi sensitive/drug-resistant gene gene levels to calculate the
Figure 02_image066
part. By integrating the corresponding weights (
Figure 02_image021
), the correlation coefficient of each gene (
Figure 02_image018
), and the precomputed weights of the relevant pathways in the PARPi response (
Figure 02_image071
) to quantify the gene-level contribution and pathway-level contribution of mutations detected in the "test gene panel" to PARPi treatment to calculate the raw composite score. The raw composite score was further adjusted and scaled according to sample type (i.e., cell line, PDX, patient) to generate the final composite score for each cancer sample (see Figure 5B and 5C row "Composite score").

5.結果和結論5. Results and conclusions

如圖5B和5C所示，當根據公式I得出的癌症樣本的綜合評分高於0時，癌症樣本確實對PARPi殺傷敏感；而當根據公式I得出的癌症樣本的綜合評分低於0時，癌症樣本確實表現出對PARPi殺傷的抗性。此外，綜合評分的絕對值越高，其對該癌症樣本的實際PARPi應答的預測能力越好(參見圖5C中基於綜合評分的“預測”行)。例如，對於綜合評分高於0.1的癌症樣本，樣本對PARPi殺傷的實際敏感性預測為“真”(參見PDX3、PDX6、PDX10、細胞株1、細胞株2和細胞株6)。對於負綜合評分較小(綜合評分的絕對值較大)的癌症樣本，樣本對PARPi殺傷的實際抗性的預測為“真”(見PDX8、細胞株4、細胞株4)。根據公式I，沒有經實際偵測敏感的癌症樣本的綜合評分低於0，這表明本文所述方法的“真陽性”預測能力很強。有一個實際偵測的敏感癌症樣本-細胞株3-的綜合評分為0。根據公式I，所有實際偵測的耐藥癌症樣本（除PDX9以外，PDX9的綜合評分為0.011）的綜合評分均低於或等於0(證明本文所述方法的“真陽性”預測能力很強)，。因此，對於綜合評分接近或等於0(例如-0.1到 +0.1)的癌症樣本，基於綜合評分對PARPi治療反應的預測是“不明確”的。可能需要進行更多評估，以根據綜合評分的預測來識別假陽性和假陰性。 As shown in Figures 5B and 5C, when the composite score of the cancer sample obtained according to Formula I is higher than 0, the cancer sample is indeed sensitive to PARPi killing; and when the composite score of the cancer sample obtained according to Formula I is lower than 0 , cancer samples did show resistance to PARPi killing. Furthermore, the higher the absolute value of the composite score, the better its predictive power of the actual PARPi response for that cancer sample (see row "Prediction" based on composite score in Figure 5C). For example, for cancer samples with a composite score above 0.1, the sample's actual sensitivity to PARPi killing was predicted to be "true" (see PDX3, PDX6, PDX10, cell line 1, cell line 2, and cell line 6). For cancer samples with a smaller negative composite score (larger absolute value of the composite score), the prediction of the sample's actual resistance to PARPi killing was "true" (see PDX8, cell line 4, cell line 4). According to Equation I, the composite score of cancer samples that were not actually detected as sensitive was below 0, which indicates that the "true positive" predictive power of the method described herein is strong. There was one sensitive cancer sample that was actually detected - cell line 3 - with a composite score of 0. According to Equation I, all actually detected drug-resistant cancer samples (except PDX9, which had a composite score of 0.011) had a composite score lower than or equal to 0 (demonstrating the strong predictive power of "true positive" of the method described in this paper) ,. Therefore, for cancer samples with a composite score close to or equal to 0 (e.g., -0.1 to +0.1 ), the prediction of response to PARPi therapy based on the composite score is 'ambiguous'. Additional evaluations may be required to identify false positives and false negatives based on the prediction of the composite score.

這些發現表明，使用本文描述的篩選方法識別的抗癌藥物(例如DNA損傷劑，如PARPi或ATRi)的藥物敏感性基因和耐藥基因，以及基於它們使用本文描述方法獲得的綜合評分，正確反映/能夠預測相應抗癌藥物的抗癌療效，並可作為癌症診斷、治療選擇和/或選擇患者的工具。例如根據公式I，當患者的綜合評分高於0時，患者可能適合(即可獲益於)抗癌藥物(例如DNA損傷劑，如PARPi或ATRi)治療。如果根據公式I，患者的綜合評分大於或等於至少0.1(例如0.3)，則可以選擇或建議患者進行抗癌藥物治療。如果根據公式I，患者的綜合評分大於0但小於0.1，則患者可能適合抗癌藥物治療，但應使用其他方法進行進一步評估(例如，藥物劑量測試、癌基因測試(例如，尋找可能有助於抗癌藥療的其他協同突變，或驗證原發癌症類型)，等)或基於其他資訊(如患者的臨床記錄或已知的耐藥性等)來確定是否應選擇或建議患者進行抗癌藥物治療。如果根據公式I，患者的綜合評分低於或等於0，則患者可能不適合(即不可獲益)或應被排除在抗癌藥物治療之外。如果在完全排除患者接受抗癌藥物治療之前，根據公式I患者的綜合評分等於0或非常接近0(例如-0.1到0)，則可能需要使用其他方法或基於本文所述的其他資訊進行進一步評估。These findings suggest that drug susceptibility and resistance genes to anticancer drugs (e.g., DNA damaging agents such as PARPi or ATRi) identified using the screening methods described herein, and the composite score based on them obtained using the methods described herein, correctly reflect / Capable of predicting the anticancer efficacy of corresponding anticancer drugs, and can be used as a tool for cancer diagnosis, treatment selection and/or patient selection. For example, according to Formula I, when the patient's composite score is higher than 0, the patient may be suitable for (ie, benefit from) anticancer drug (eg, DNA damaging agent, such as PARPi or ATRi) treatment. If according to Formula I, the patient's composite score is greater than or equal to at least 0.1 (eg, 0.3), the patient may be selected or recommended for anticancer drug treatment. If the patient's composite score according to Equation I is greater than 0 but less than 0.1, the patient may be a candidate for anticancer drug therapy but should be further evaluated using other methods (e.g., drug dose testing, oncogene testing (e.g., looking for other synergistic mutations of anticancer drugs, or verify the primary cancer type), etc.) or based on other information (such as the patient's clinical records or known drug resistance, etc.) to determine whether anticancer drugs should be selected or recommended for patients treat. If according to Equation I, the patient's composite score is less than or equal to 0, the patient may not be suitable (ie, not benefit) or should be excluded from anticancer drug treatment. If a patient's composite score according to Equation I equals 0 or is very close to 0 (eg, -0.1 to 0) before the patient is completely excluded from anticancer drug therapy, further evaluation using other methods or based on other information described herein may be warranted .

無none

圖1顯示了篩選抗癌藥物的藥物敏感性和/或耐藥基因的示例性步驟。 圖2顯示了Cas9 +sgRNA iBAR癌細胞庫的示例性篩選工作流程。 圖3顯示了Cas9 +sgRNA iBAR癌細胞庫的示例性靶基因鑒定工作流程。 圖4顯示了藥物敏感性基因或耐藥基因敲除(KO)的癌細胞的PARPi應答曲線。用PARPi處理的沒有這種KO的癌細胞(WT)用作對照。 圖5A顯示了16個癌症樣本中PARPi的藥物敏感性基因和耐藥基因(y軸，總共51個基因)的功能喪失(LOF)突變概率。圖5B顯示了使用公式I基於每個癌症樣本的51個基因計算的綜合評分。圖5C顯示了針對每個癌症樣本的綜合評分、對PARPi治療的應答和基於綜合評分的治療功效預測。 Figure 1 shows exemplary steps for screening drug sensitivity and/or drug resistance genes of anticancer drugs. Figure 2 shows an exemplary screening workflow for the Cas9 + sgRNA iBAR cancer cell library. Figure 3 shows an exemplary target gene identification workflow for the Cas9 + sgRNA iBAR cancer cell bank. Figure 4 shows the PARPi response curves of cancer cells with drug-sensitive or drug-resistant gene knockout (KO). Cancer cells without this KO (WT) treated with PARPi were used as controls. Figure 5A shows the loss-of-function (LOF) mutation probabilities of PARPi's drug-sensitivity genes and drug-resistant genes (y-axis, 51 genes in total) in 16 cancer samples. Figure 5B shows the composite score calculated using Formula I based on 51 genes for each cancer sample. Figure 5C shows the composite score for each cancer sample, the response to PARPi treatment and the prediction of treatment efficacy based on the composite score.

Claims (34)

一種治療個體結直腸癌的方法，包含向所述個體投予有效量的DNA損傷劑，其中選擇所述個體進行治療的依據是，來自所述個體的樣本在一個或多個選自下組的藥物敏感性基因中具有一種或多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B。A method of treating colorectal cancer in an individual, comprising administering to the individual an effective amount of a DNA damaging agent, wherein the individual is selected for treatment based on a sample from the individual in one or more of the group consisting of One or more drug sensitivity abnormalities in drug sensitivity genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, Z NF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B. 如請求項1所述的方法，其中選擇所述個體進行治療的依據是，來自所述個體的樣本中藥物敏感性異常和耐藥異常的綜合評分高於閾值水準，其中所述耐藥異常是一個或多個選自下組的耐藥基因中的一種或多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。The method according to claim 1, wherein the basis for selecting the individual for treatment is that the combined score of drug sensitivity abnormality and drug resistance abnormality in the sample from the individual is higher than a threshold level, wherein the drug resistance abnormality is One or more resistance abnormalities in one or more resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR , CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1 , IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1 , SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY , CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A , KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1 , MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1 , MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC 5. RET , SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras , CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. 如請求項1或2所述的方法，其還包含在投予DNA損傷劑之前從來自所述個體的樣本中獲知一個或多個選自下組的藥物敏感基因中的一種或多種藥物敏感性異常： PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或者多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。The method according to claim 1 or 2, further comprising knowing one or more drug sensitivity in one or more drug sensitive genes selected from the group below from a sample from the individual before administering the DNA damaging agent Exception: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP 90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance abnormalities in one or more drug resistance genes selected from the group: PARP1, MAPK1 , TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A , VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1 , SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6 , KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7 , NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MyH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, Foxg1, Arid1a, TSC1, Smad2, CCDC, CCDCC1, Smad2, CCDCC1 168, MyH2, MDM2, Dusp5, NCK1, APC , VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4 , PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1 , CCNE1, Dock1, Znf469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, Kiaa1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A,, SCN3A, SCN3A, Dock6, ROCK2, COMP, Arid2, RHOA, JPH3 , TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. 如請求項3所述的方法，其中所述獲知包含獲得所述個體的樣本中藥物敏感性異常和耐藥異常的綜合評分。The method according to claim 3, wherein said learning comprises obtaining a comprehensive score of abnormal drug sensitivity and abnormal drug resistance in the sample of the individual. 如請求項3或4所述的方法，其中，所述獲知一種或多種藥物敏感性異常和/或一種或多種耐藥異常包含偵測所述樣本中一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。The method as claimed in claim 3 or 4, wherein the knowing one or more drug sensitivity abnormalities and/or one or more drug resistance abnormalities comprises detecting one or more drug sensitive drug selected from the following group in the sample One or more drug sensitivity abnormalities in sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF56 8. FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance genes selected from the following group One or more drug resistance abnormalities: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1 , RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1 , SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA , DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP , RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC1 68 , MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2 , MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1 , ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN 3A, DOCK6 , ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. 一種鑒定可獲益於包含投予DNA損傷劑的治療的患有結直腸癌的個體的方法，所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或者多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，其中，在所述樣本中一種或多種藥物敏感性異常的存在，表明所述個體是可從所述治療中獲益的個體。A method of identifying an individual with colorectal cancer who may benefit from a treatment comprising administering a DNA damaging agent, said method comprising detecting in a sample from said individual one or more drug sensitive agents selected from the group consisting of: One or more drug sensitivity abnormalities in sex genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF56 8. FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, wherein the presence of one or more drug sensitivity abnormalities in said sample, The individual is shown to be one who would benefit from the treatment. 如請求項6所述的方法，其中所述方法包含在來自所述個體的樣本中偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，以及一個或多個選自下組的耐藥基因中的一種或多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1，其中，高於閾值水準的藥物敏感性異常和耐藥異常的綜合評分表明所述患者是可從治療中獲益的個體。The method according to claim 6, wherein said method comprises detecting one or more drug sensitivity abnormalities in one or more drug sensitivity genes selected from the group consisting of PTEN, CAB39 in a sample from said individual , RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2 , DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B , TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2 , WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1 , CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30 , ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2 , DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42 , DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTO A , DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B , RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and one or more drug resistance abnormalities in one or more drug resistance genes selected from the group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TEN M3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1, among which, the combined score of abnormal drug sensitivity and abnormal drug resistance above the threshold level indicates that The patient is an individual who would benefit from treatment. 如請求項5-7中任一項所述的方法，其中，所述偵測一個或多個藥物敏感性基因中的一種或多種藥物敏感性異常和/或一個或多個耐藥基因中的一種或多種耐藥異常包括對多個藥物敏感性基因和/或耐藥基因或其相關部分進行定序。The method according to any one of claims 5-7, wherein the detection of one or more drug sensitivity abnormalities in one or more drug sensitivity genes and/or one or more drug resistance genes One or more drug resistance abnormalities includes sequencing multiple drug sensitivity genes and/or drug resistance genes or relative portions thereof. 如請求項1-8中任一項所述的方法，其中所述DNA損傷劑是PARPi或ATRi。The method of any one of claims 1-8, wherein the DNA damaging agent is PARPi or ATRi. 如請求項9所述的方法，其中所述DNA損傷劑是PARPi。The method of claim 9, wherein the DNA damaging agent is PARPi. 如請求項10所述的方法，其中所述一個或多個藥物敏感性基因選自下組：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1。The method as claimed in claim 10, wherein the one or more drug sensitive genes are selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7 , CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1 , DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM , PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13 , TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1. 如請求項10或11所述的方法，其中所述一個或多個藥物敏感性基因選自下組：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX。The method as claimed in item 10 or 11, wherein said one or more drug sensitivity genes are selected from the group consisting of: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1 , WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7 , TGFB2, TSC1 , TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX. 如請求項10-12中任一項所述的方法，其中所述一個或多個耐藥基因選自下組：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。The method according to any one of claims 10-12, wherein the one or more drug resistance genes are selected from the group consisting of PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. 如請求項10-13中任一項所述的方法，其中所述一個或多個耐藥基因選自下組：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。The method according to any one of claims 10-13, wherein the one or more drug resistance genes are selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. 如請求項9所述的方法，其中所述DNA損傷劑是ATRi。The method of claim 9, wherein the DNA damaging agent is ATRi. 如請求項15所述的方法，其中所述一個或多個藥物敏感性基因選自下組：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B。The method according to claim 15, wherein the one or more drug sensitive genes are selected from the group consisting of ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1 , DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4 , NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2 , GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1 , TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB 2. CR1 , FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2 , APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B. 如請求項15或16所述的方法，其中所述一個或多個耐藥基因選自下組：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。The method according to claim 15 or 16, wherein the one or more drug-resistant genes are selected from the group consisting of RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G 2. DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1 . 如請求項1-17中任一項所述的方法，其中所述結直腸癌是晚期結腸癌，惡性結腸癌，轉移性結腸癌，I期、II期、III期或IV期結腸癌，以基因組不穩定為特徵的結腸癌，或以通路改變為特徵的結腸癌。The method of any one of claims 1-17, wherein the colorectal cancer is advanced colon cancer, malignant colon cancer, metastatic colon cancer, stage I, stage II, stage III or stage IV colon cancer, and Colon cancer characterized by genomic instability, or colon cancer characterized by pathway alterations. 如請求項1-18中任一項所述的方法，其中所述個體曾接受過治療。The method of any one of claims 1-18, wherein the individual has received treatment. 如請求項1-19中任一項所述的方法，其中所述樣本是腫瘤活檢樣本、迴圈腫瘤細胞樣本或固定的組織樣本。The method according to any one of claims 1-19, wherein the sample is a tumor biopsy sample, a loop tumor cell sample or a fixed tissue sample. 如請求項1-20中任一項所述的方法，其中在對異常分析之前，從所述樣本中選擇性增濃包含一個或多個藥物敏感性基因和/或一個或多個耐藥基因的核酸或由一個或多個藥物敏感性基因和/或一個或多個耐藥基因編碼的多肽。The method according to any one of claims 1-20, wherein the selective enrichment of one or more drug-susceptibility genes and/or one or more drug-resistant genes from the sample is performed prior to abnormal analysis Nucleic acid or polypeptide encoded by one or more drug sensitivity genes and/or one or more drug resistance genes. 如請求項1-21中任一項所述的方法，其中所述一種或多種藥物敏感性異常和/或一種或多種耐藥異常包括一個或更多個核苷酸的插入、刪除或替換，基因組重排，啟動子的改變，基因融合，或拷貝數改變中的一種或多種。The method according to any one of claims 1-21, wherein the one or more drug sensitivity abnormalities and/or one or more drug resistance abnormalities comprise insertions, deletions or substitutions of one or more nucleotides, One or more of genomic rearrangements, promoter alterations, gene fusions, or copy number alterations. 如請求項1-22中任一項所述的方法，其中所述個體是人。The method of any one of claims 1-22, wherein the individual is a human. 多個捕獲核酸分子，其被配置成與選自下組的多個藥物敏感性基因雜交：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或與選自下組的多個耐藥基因雜交：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。A plurality of capture nucleic acid molecules configured to hybridize to a plurality of drug sensitivity genes selected from the group consisting of PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK 14. PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、 TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or with optional Multiple resistance gene hybridization from the following group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2 , PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1 , BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1 , CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1 , PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1 , SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B , FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT , PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1 , SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1. 如請求項24所述的多個捕獲核酸分子，其中所述多個捕獲核酸分子的每一個包含約10到約200個核苷酸。The plurality of capture nucleic acid molecules of claim 24, wherein each of the plurality of capture nucleic acid molecules comprises about 10 to about 200 nucleotides. 如請求項24或25所述的多個捕獲核酸分子，其中所述多個捕獲核酸分子的每一個偶聯到親和試劑或偵測試劑上。A plurality of capture nucleic acid molecules as claimed in claim 24 or 25, wherein each of the plurality of capture nucleic acid molecules is coupled to an affinity reagent or a detection reagent. 如請求項24-26中任一項所述的多個捕獲核酸分子，其中所述多個捕獲核酸分子配置為與選自下組的多個藥物敏感性基因雜交：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或與選自下組的多個耐藥基因雜交：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。A plurality of capture nucleic acid molecules as described in any one of claims 24-26, wherein the plurality of capture nucleic acid molecules are configured to hybridize with a plurality of drug sensitivity genes selected from the group: PTEN, CAB39, RIF1, STAG1 , ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1 , NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1 , ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4 , RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL , EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or hybridize with a plurality of drug resistance genes selected from the group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. 如請求項24-27中任一項所述的多個捕獲核酸分子，其中所述多個捕獲核苷酸分子被配置為與選自下組的多個藥物敏感性基因雜交：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或與選自下組的多個耐藥基因雜交：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。A plurality of capture nucleic acid molecules as described in any one of claim items 24-27, wherein the plurality of capture nucleotide molecules are configured to hybridize with a plurality of drug sensitivity genes selected from the group: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and/or with a plurality of selected from the group Drug resistance gene hybridization: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2, DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1 , CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5, E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. 如請求項24-26中任一項所述的多個捕獲核酸分子，其中所述多個捕獲核苷酸分子被配置為與選自下組的多個藥物敏感性基因雜交：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或與選自下組的多個耐藥基因雜交：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。A plurality of capture nucleic acid molecules as described in any one of claim items 24-26, wherein the plurality of capture nucleic acid molecules are configured to hybridize with a plurality of drug sensitivity genes selected from the group: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, ACTA1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, Kiaa1109, MGA, Dok5, STK11, NFE2L1, ENC1, HDAC2, Gucy2D, Adamts2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, CSNK1G1, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11 , WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B , and/or hybridize with a plurality of drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2 , RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1, FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D , TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1 , JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34 , PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A , DOCK6 , ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, and GAB1. 如請求項一種系統，其包含：被配置為存儲一個或更多個程式指令的記憶體；和一個或更多個被配置為執行所述一個或多個程式指令的處理器，其中所述一個或多個程式指令在由一個或多個處理器執行時被配置為：(a)獲得一種或多種核酸或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長以分析在一個或多個選自下組的藥物敏感性基因中是否存在一種或多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或在一個或多個選自下組的耐藥基因中是否存在一種或多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。A system as claimed, comprising: a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions, wherein the one The or more program instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a patient with A sample obtained from an individual with colorectal cancer; (b) analyzing the plurality of sequence reads for the presence of one or more drug sensitivity abnormalities in one or more drug sensitivity genes selected from the group consisting of: PTEN, CAB39 , RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2 , DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B , TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2 , WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1 , CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30 , ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2 , DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42 , DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTO A , DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B , RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or whether there is one or more drug resistance abnormalities in one or more drug resistance genes selected from the group: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13 C. PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, Dock1, Znf469, PLA2G12B, EGFR, WDFY4, USP9X, Gal3st4, Kiaa1217, Mapk3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, R OCK2, COMP, Arid2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1; and (c) detecting one or more candidate genes based on the analysis One or more drug sensitivity abnormalities in drug sensitivity genes from the following group: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS 2. ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C , CDKN1A, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more selected from the following group One or more resistance abnormalities in the resistance genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8 , PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2 , FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR , XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B , EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR 1 , TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5 , CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4 , POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2 , DBF4 , CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2 , and GAB1. 一種系統，其包含：被配置為存儲一個或更多個程式指令的記憶體；和一個或更多個被配置為執行所述一個或多個程式指令的處理器，其中所述一個或多個程式指令在由一個或多個處理器執行時被配置為：(a)獲得一種或多種核酸或多肽的多個序列讀長，其中所述一種或多種核酸或多肽來源於從患有結直腸癌的個體獲得的樣本；(b)分析所述多個序列讀長以分析在一個或多個選自下組的藥物敏感性基因中是否存在一種或多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或在一個或多個選自下組的耐藥基因中是否存在一種或多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1；和(c)基於所述分析偵測一個或多個選自下組的藥物敏感性基因中的一種或多種藥物敏感性異常：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、STAP1、POLA1、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、EP300、KIF13A、TNF、LRP5、IL18、RNF213、EML5、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、MXD4、ANK2、NOG、KIAA1109、DOK5、STK11、ENC1、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、HSP90AB1、CKS2、ANAPC7、DIDO1、ACTB、TP53BP1、LRRIQ1、NALCN、MRGBP、HSP90AA1、PAK1、CDC42、DLGAP2、AKAP12、LARP4B、KAT2A、BCL2L1、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和HLA-B，和/或一個或多個選自下組的耐藥基因中的一種或多種耐藥異常：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、FGF19、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、MDM2、DUSP5、NCK1、APC、VPS13C、PLA2G6、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、FMN2、FANCB、DMXL2、CSNK1D、TIAM1、MTOR、PDPK1、PML、LAMA5、CDC25B、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、OPLAH、CCND2、PLA2G3、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、CSNK2A1、USP34、PBRM1、FZD1、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、EIF4G2、DBF4、CTNNBIP1、SCN3A、DOCK6、ROCK2、COMP、ARID2、RHOA、JPH3、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和GAB1。A system comprising: a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions, wherein the one or more The program instructions, when executed by the one or more processors, are configured to: (a) obtain a plurality of sequence reads of one or more nucleic acids or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from patients with colorectal cancer (b) analyzing the plurality of sequence reads to analyze whether there is one or more drug sensitivity abnormalities in one or more drug sensitivity genes selected from the group: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5, MXD4, ANK2, NOG, KIAA1109, DOK5, STK11, ENC1, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, HSP90AB1, CKS2, ANAPC7, DIDO1, ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2 , AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568, FGF23, PEG3, HPRT1, DNAH11, DPM2, DPM2, DPM2 , PTPN11, Wnt7b, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or the presence or absence of one or more drug resistance abnormalities in one or more drug resistance genes selected from the group consisting of: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1 , CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4 , RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1 , HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1 , MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L , WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3 , PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1 , OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469 , PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CTNNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4 , MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1; and (c) detect one or more selected from the group consisting of Abnormal drug sensitivity in one or more of the drug sensitivity genes: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12 , TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A , BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A , YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1 , NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, STAP1, POLA1, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, EP300, KIF13A, TNF, LRP5, IL18, RNF213, EML5 , TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, ROBO2, NFATC4, NCAM1, MAML1, NUMB, PHLDA2, FOXO3, NAV2, RAC3, TSPAN1, RPS6KA2, CHEK2, CSNK1E, YWHAB, ID4, ADAMTS5 . 、DIDO1 , ACTB, TP53BP1, LRRIQ1, NALCN, MRGBP, HSP90AA1, PAK1, CDC42, DLGAP2, AKAP12, LARP4B, KAT2A, BCL2L1, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, ZNF568 , FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3 , FASLG, DNAH10, MAPK12, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and HLA-B, and/or one or more drug resistance selected from the group One or more resistance abnormalities in genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1, USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1, CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2, BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3, ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, FGF19, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A, CIR1, TSC1, SMAD2, CCDC168, MYH2, MDM2, DUSP5, NCK1, APC, VPS13C, PLA2G6, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, FMN2, FANCB, DMXL2, CSNK1D, TIAM1, MTOR, PDPK1, PML, LAMA5, CDC25B, FGFR3, THBS2, MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, OPLAH, CCND2, PLA2G3, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4, POLRMT, PLCE1, E2F1, ID2, CSNK2A1, USP34, PBRM1, FZD1, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD4, EIF4G2, DBF4, CT NNBIP1, SCN3A, DOCK6, ROCK2, COMP, ARID2, RHOA, JPH3, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH, AMOTL2, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and GAB1 . 如請求項30所述的系統或根據請求項31所述的非暫時性電腦可讀存儲介體，其中所述一種或多種藥物敏感性異常位於一個或多個選自下組的藥物敏感性基因中：PTEN、CAB39、RIF1、STAG1、ABCC1、TSC1、FBXW7、ATM、UBE2T、FBXW11、MGA、DUSP4、CHD7、CDC25B、SKP2、NF2、GSK3B、TRIP12、TSC2、FANCB、POLQ、KDM5C、NBN、DDIT4、CDCA7、KIDINS220、CDK2、DTX2、ELAVL1、NFAT5、EIF4E2、RFX7、ATR、MYO9B、CUL1、PRKAA1、SCAF4、NFE2L1、DNTTIP1、NIPBL、HRAS、RBM10、GSK3A、BAZ1A、CCNA2、BRCA1、HDAC2、USP9X、AMOTL2、AXIN1、SMAD5、KAT2B、TGFB2、GFRA1、ARAP2、ARNT、NCK1、ACTA1、CIR1、CBFB、DROSHA、RUNX1、FANCM、PBRM1、DOT1L、BIRC6、RBM15、SEC16A、YWHAE、ETV4、UBR5、DUSP5、SCN11A、YLPM1、DSCAM、ASXL1、ARID2、WEE1、DBF4、RUNX2、PJA2、CCND1、DICER1、RBPJ、BRCA2、ZFHX3、ZEB1、ZC3H13、TRAIP、SMAD7、LATS2、USP34、E2F1、NRAS、HOXB8、CD14、PLXNB2、FAM73B、WDR87、PPARD、LRBA、FAM71A、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、和STAP1，和/或一種或多種耐藥異常位於一個或多個選自下組的耐藥基因中：PARP1、MAPK1、TCF7L2、MLST8、HSP90B1、CKS2、TP53、CDKN1A、MAPK14、TP53BP1、CRKL、RHEB、CTNNB1、MYC、RICTOR、CHP1、EIF1、LARP4B、ZMYND8、PTK2、PIK3CA、RAC1、RAPGEF1、RAF1、USP28、PSENEN、EIF3A、VHL、GNA11、SMAD4、RPTOR、NCOR2、MAP3K4、ID1、TEAD1、EIF4B、PXN、PRKAR1A、BRAF、WWTR1、IGF1R、NCSTN、PIK3R2、PARP2、FOSL1、BMPR1A、IRS1、SRC、RBL1、CHD2、AKT1、YES1、SMARCA2、DPM2、RPS6KB1、HES1、MED12、YAP1、ILK、PPP2R1A、SP1、EIF2B2、DLG5、BUB1、CCNA1、SPTA1、GCN1L1、EP300、EPOR、XIRP1、CDH11、INHA、DOCK5、SETD2、BNIPL、ANK1、AKAP6、KMT2B、E2F4、VAV1、MYO16、ACVRL1、KCNH1、PDRG1、IKBKG、PLA2G2C、MUC4、RPS6KB2、HIF1A、FRY、CR1、EPHA5、BCAR1、CKS1B、EIF4A1、PLEC、CREBBP、RELA、E2F3、ITIH6、BRPF3、ANAPC7、NFKBIA、HDAC1、CSE1L、WWC3、NPM1、MYH14、RASL10B、MYH9、Kras、CDKN2A、CHEK1、PKMYT1、SIDT2、和FGF19。The system according to claim 30 or the non-transitory computer-readable storage medium according to claim 31, wherein the one or more drug sensitivity abnormalities are located in one or more drug sensitivity genes selected from the group below Medium: PTEN, CAB39, RIF1, STAG1, ABCC1, TSC1, FBXW7, ATM, UBE2T, FBXW11, MGA, DUSP4, CHD7, CDC25B, SKP2, NF2, GSK3B, TRIP12, TSC2, FANCB, POLQ, KDM5C, NBN, DDIT4, CDCA7, KIDINS220, CDK2, DTX2, ELAVL1, NFAT5, EIF4E2, RFX7, ATR, MYO9B, CUL1, PRKAA1, SCAF4, NFE2L1, DNTTIP1, NIPBL, HRAS, RBM10, GSK3A, BAZ1A, CCNA2, BRCA1, HDAC2, USP9X, AMOTL2, AXIN1, SMAD5, KAT2B, TGFB2, GFRA1, ARAP2, ARNT, NCK1, ACTA1, CIR1, CBFB, DROSHA, RUNX1, FANCM, PBRM1, DOT1L, BIRC6, RBM15, SEC16A, YWHAE, ETV4, UBR5, DUSP5, SCN11A, YLPM1, DSCAM, ASXL1, ARID2, WEE1, DBF4, RUNX2, PJA2, CCND1, DICER1, RBPJ, BRCA2, ZFHX3, ZEB1, ZC3H13, TRAIP, SMAD7, LATS2, USP34, E2F1, NRAS, HOXB8, CD14, PLXNB2, FAM73B, WDR87, PPARD, LRBA, FAM71A, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, and STAP1, and/or one or more drug resistance abnormalities are located in one or more drug resistance selected from the group Among genes: PARP1, MAPK1, TCF7L2, MLST8, HSP90B1, CKS2, TP53, CDKN1A, MAPK14, TP53BP1, CRKL, RHEB, CTNNB1, MYC, RICTOR, CHP1, EIF1, LARP4B, ZMYND8, PTK2, PIK3CA, RAC1, RAPGEF1, RAF1 , USP28, PSENEN, EIF3A, VHL, GNA11, SMAD4, RPTOR, NCOR2, MAP3K4, ID1, TEAD1, EIF4B, PXN, PRKAR1A, BRAF, WWTR1, IGF1R, NCSTN, PIK3R2, PARP2, FOSL1, BMPR1A, IRS1, SRC, RBL1 , CHD2, AKT1, YES1, SMARCA2, DPM2, RPS6KB1, HES1, MED12, YAP1, ILK, PPP2R1A, SP1, EIF2B2, DLG5, BUB1, CCNA1, SPTA1, GCN1L1, EP300, EPOR, XIRP1, CDH11, INHA, DOCK5, SETD2 , BNIPL, ANK1, AKAP6, KMT2B, E2F4, VAV1, MYO16, ACVRL1, KCNH1, PDRG1, IKBKG, PLA2G2C, MUC4, RPS6KB2, HIF1A, FRY, CR1, EPHA5, BCAR1, CKS1B, EIF4A1, PLEC, CREBBP, RELA, E2F3 , ITIH6, BRPF3, ANAPC7, NFKBIA, HDAC1, CSE1L, WWC3, NPM1, MYH14, RASL10B, MYH9, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19. 如請求項30或32所述的系統或根據請求項31或32所述的非暫時性電腦可讀存儲介體，其中所述一種或多種藥物敏感性異常位於一個或多個選自下組的藥物敏感性基因中：ATM、ATR、BIRC6、BRCA1、FANCM、NBN、STAG1、ARID2、CHD7、POLQ、PTEN、RIF1、WEE1、DIDO1、RAD51、FANCL、EXO1、RAD51B、RAD51C、RAD51D、PMS2、MSH6、MSH2、MLH1、LRBA、FAM71A、BRCA2、HDAC2、CCNA2、CCND1、CDK2、FBXW7、HRAS、KAT2B、PBRM1、SKP2、SMAD7、TGFB2、TSC1、TSC2、AXIN1、GSK3A、GSK3B、SCAF4、NIPBL、和ATRX，和/或所述一種或多種耐藥異常位於一個或多個選自下組的耐藥基因中：PARP1、TP53、CTNNB1、MYC、RICTOR、EIF3A、ZMYND8、MED12、SETD2、GCN1、Kras、TP53BP1、CHD2、DOCK5、IGF1R、ILK、IRS1、RAPGEF1、EP300、TCF7L2、KMT2B、CDKN2A、CHEK1、CHEK2、RHEB、SPTA1、PKMYT1、SIDT2、PARP2、PIK3CA、BRAF、SMAD4、APC、AKT1、CDKN1A、CKS1B、CKS2、DLG5、E2F3、E2F4、HDAC1、MAPK1、RAC1、HSP90B1、CCNA1、和RBL1。The system according to claim 30 or 32 or the non-transitory computer-readable storage medium according to claim 31 or 32, wherein the one or more drug sensitivity abnormalities are located in one or more selected from the group Drug sensitivity genes: ATM, ATR, BIRC6, BRCA1, FANCM, NBN, STAG1, ARID2, CHD7, POLQ, PTEN, RIF1, WEE1, DIDO1, RAD51, FANCL, EXO1, RAD51B, RAD51C, RAD51D, PMS2, MSH6, MSH2, MLH1, LRBA, FAM71A, BRCA2, HDAC2, CCNA2, CCND1, CDK2, FBXW7, HRAS, KAT2B, PBRM1, SKP2, SMAD7, TGFB2, TSC1, TSC2, AXIN1, GSK3A, GSK3B, SCAF4, NIPBL, and ATRX, and /or the one or more drug resistance abnormalities are located in one or more drug resistance genes selected from the group consisting of: PARP1, TP53, CTNNB1, MYC, RICTOR, EIF3A, ZMYND8, MED12, SETD2, GCN1, Kras, TP53BP1, CHD2 , DOCK5, IGF1R, ILK, IRS1, RAPGEF1, EP300, TCF7L2, KMT2B, CDKN2A, CHEK1, CHEK2, RHEB, SPTA1, PKMYT1, SIDT2, PARP2, PIK3CA, BRAF, SMAD4, APC, AKT1, CDKN1A, CKS1B, CKS2, DLG5 , E2F3, E2F4, HDAC1, MAPK1, RAC1, HSP90B1, CCNA1, and RBL1. 如請求項30所述的系統或根據請求項31所述的非暫時性電腦可讀存儲介體，其中所述一種或多種藥物敏感性異常位於一個或多個選自下組的藥物敏感性基因中：ATR、YWHAE、NBN、WEE1、POLA1、ATM、CDK12、CKS1B、PRKDC、ARRB1、PRDM10、HES1、SKAP1、DSEL、EIF1、BAZ1A、EP300、GSK3B、KIF13A、TNF、LRP5、IL18、RNF213、EML5、ACTA1、FBXW11、TGFBI、DSCAML1、EIF4A2、DNAH17、LAMA4、KANSL1、NRXN2、DTX4、SAP30、PRKAA1、ROBO2、NFATC4、NCAM1、MAML1、NUMB、PHLDA2、FOXO3、NAV2、RAC3、TSPAN1、RPS6KA2、CHEK2、CSNK1E、YWHAB、ID4、ADAMTS5、DSCAM、MXD4、ANK2、NOG、KIAA1109、MGA、DOK5、STK11、NFE2L1、ENC1、HDAC2、GUCY2D、ADAMTS2、DLEC1、HSPG2、TRIB3、PLA2G2D、GDF7、TCF7L2、CSNK1G1、DSP、RPS6KA5、BMP8B、MAPK14、PARP2、PTEN、GSK3A、POLQ、HSP90AB1、CHD7、CKS2、ANAPC7、DIDO1、CDK2、ACTB、GFRA1、TP53BP1、LRRIQ1、STAG1、ZFHX3、NALCN、MRGBP、MYO9B、HSP90AA1、PAK1、YLPM1、CDC42、DLGAP2、FBXW7、ABCC1、AKAP12、LARP4B、KAT2A、BCL2L1、KDM5C、MAGI2、PTP4A3、PARP14、AXL、GRB2、CR1、FOXO1、TGFB1、TENM4、PLA2G2C、CDKN1A、SMAD7、ZNF568、FGF23、PEG3、INS、HPRT1、DNAH11、DPM2、PTPN11、WNT7B、OTOA、DNTTIP1、DTX1、ALK、TSHZ3、FGFR4、FGF2、CSF1、EPHA5、TFPI2、APCDD1、FCGBP、FANCM、PTPRR、PMS1、USP28、LAMB1、UNC13C、WWC3、FASLG、DNAH10、MAPK12、和HLA-B，和/或一種或多種耐藥異常位於一個或多個選自下組的耐藥基因中：RHEB、MED12、PRKAR1A、EIF4E2、TNFRSF17、CUL9、CDC25A、KMT2D、FOXG1、ARID1A、CIR1、TSC1、SMAD2、CCDC168、MYH2、CHD2、MDM2、RICTOR、DUSP5、SMAD4、SETD2、NCK1、RAF1、APC、VPS13C、ACVRL1、PLA2G6、TP53、TENM3、PPP2R1B、BMP7、STRADA、ADGRB2、NRG1、CTNNB1、FMN2、FANCB、PARP1、DMXL2、CHP1、IKBKG、CSNK1D、TIAM1、EIF4B、RPTOR、MLST8、E2F3、MYC、MTOR、PIK3CA、PDPK1、PML、PIK3R2、IGF1R、MAPK1、LAMA5、CDC25B、CRKL、FGFR3、THBS2、MUC5B、DOT1L、CCND1、DVL1、IRS4、PDK2、PLCG1、JAK1、VAV1、OPLAH、CCND2、RAPGEF1、PLA2G3、AKT1、KIAA0556、CACNG8、CCNA2、NF2、CDK1、SBNO1、CDH1、MT2A、FAM21C、CHUK、DOK4、POLRMT、PLCE1、E2F1、ID2、PSENEN、CSNK2A1、USP34、PBRM1、FZD1、SRC、CCNE1、DOCK1、ZNF469、PLA2G12B、EGFR、WDFY4、USP9X、GAL3ST4、KIAA1217、MAPK3、CBFB、NLRC5、RET、SKP2、BRD4、MYH9、EIF4G2、DBF4、CTNNBIP1、GNA11、SCN3A、DOCK6、ROCK2、EPOR、COMP、ARID2、RHOA、JPH3、ID1、TFDP1、FRYL、EPHB4、MATK、DNMT3B、FREM2、ADAMTS18、DDIT4、MUC17、CUL1、PTPRH、AMOTL2、和GAB1。The system according to claim 30 or the non-transitory computer-readable storage medium according to claim 31, wherein the one or more drug sensitivity abnormalities are located in one or more drug sensitivity genes selected from the group below Medium: ATR, YWHAE, NBN, WEE1, POLA1, ATM, CDK12, CKS1B, PRKDC, ARRB1, PRDM10, HES1, SKAP1, DSEL, EIF1, BAZ1A, EP300, GSK3B, KIF13A, TNF, LRP5, IL18, RNF213, EML5, Acta1, FBXW11, TGFBI, DSCAML1, EIF4A2, DNAH17, LAMA4, KANSL1, NRXN2, DTX4, SAP30, PRKAA1, Robo2, NCAM1, MAML1, PHLDA2, Foxo3, NAV, NAV, NAV, NAV 2. RAC3, TSPAN1, RPS6KA2, Chek2, CSNK1E, YWHAB, ID4, ADAMTS5, DSCAM, MXD4, ANK2, NOG, KIAA1109, MGA, DOK5, STK11, NFE2L1, ENC1, HDAC2, GUCY2D, ADAMTS2, DLEC1, HSPG2, TRIB3, PLA2G2D, GDF7, TCF7L2, CSNK1G1, DSP, RPS6KA5, BMP8B, MAPK14, PARP2, PTEN, GSK3A, POLQ, HSP90AB1, CHD7, CKS2, ANAPC7, DIDO1, CDK2, ACTB, GFRA1, TP53BP1, LRRIQ1, STAG1, ZFHX3, NALCN, MRGBP, MYO9B, HSP90AA1, PAK1, YLPM1, CDC42, DLGAP2, FBXW7, ABCC1, AKAP12, LARP4B, KAT2A, BCL2L1, KDM5C, MAGI2, PTP4A3, PARP14, AXL, GRB2, CR1, FOXO1, TGFB1, TENM4, PLA2G2C, CDKN1A, SMAD7,, SMAD7,, SMAD7,, SMAD7,, SMAD7, SMAD7,, SMAD7, SMAD7,, SMAD7,, Smad7, SMAD7,, Smad7, SMAD7, SMAD7, SMAD7, ZNF568, FGF23, PEG3, INS, HPRT1, DNAH11, DPM2, PTPN11, WNT7B, OTOA, DNTTIP1, DTX1, ALK, TSHZ3, FGFR4, FGF2, CSF1, EPHA5, TFPI2, APCDD1, FCGBP, FANCM, PTPRR, PMS1, USP28, LAMB1, UNC13C, WWC3, FASLG, DNAH10, MAPK12, and HLA-B, and/or one or more drug resistance abnormalities located in one or more drug resistance genes selected from the group consisting of: RHEB, MED12, PRKAR1A, EIF4E2, TNFRSF17, CUL9, CDC25A, KMT2D, FOXG1, ARID1A , CIR1, TSC1, SMAD2, CCDC168, MYH2, CHD2, MDM2, RICTOR, DUSP5, SMAD4, SETD2, NCK1, RAF1, APC, VPS13C, ACVRL1, PLA2G6, TP53, TENM3, PPP2R1B, BMP7, STRADA, ADGRB2, NRG1, CTNNB1 , FMN2, FANCB, PARP1, DMXL2, CHP1, IKBKG, CSNK1D, TIAM1, EIF4B, RPTOR, MLST8, E2F3, MYC, MTOR, PIK3CA, PDPK1, PML, PIK3R2, IGF1R, MAPK1, LAMA5, CDC25B, CRKL, FGFR3, THBS2 , MUC5B, DOT1L, CCND1, DVL1, IRS4, PDK2, PLCG1, JAK1, VAV1, OPLAH, CCND2, RAPGEF1, PLA2G3, AKT1, KIAA0556, CACNG8, CCNA2, NF2, CDK1, SBNO1, CDH1, MT2A, FAM21C, CHUK, DOK4 , POLRMT, PLCE1, E2F1, ID2, PSENEN, CSNK2A1, USP34, PBRM1, FZD1, SRC, CCNE1, DOCK1, ZNF469, PLA2G12B, EGFR, WDFY4, USP9X, GAL3ST4, KIAA1217, MAPK3, CBFB, NLRC5, RET, SKP2, BRD 4 , MYH9, EIF4G2, DBF4, CTNNBIP1, GNA11, SCN3A, DOCK6, ROCK2, EPOR, COMP, ARID2, RHOA, JPH3, ID1, TFDP1, FRYL, EPHB4, MATK, DNMT3B, FREM2, ADAMTS18, DDIT4, MUC17, CUL1, PTPRH , AMOTL2, and GAB1.
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