WO2023284736A1

WO2023284736A1 - Biomarkers for colorectal cancer treatment

Info

Publication number: WO2023284736A1
Application number: PCT/CN2022/105194
Authority: WO
Inventors: Pengfei YUAN; Ming Jin; Yongjian Zhang; Hongyan Shen; Ling Yang; Na LIU; Meihua SU; Yaru Zheng; Yulan Li
Original assignee: Edigene Therapeutics (Beijing) Inc.
Priority date: 2021-07-12
Filing date: 2022-07-12
Publication date: 2023-01-19
Also published as: WO2023284735A1; TW202317523A; TW202309299A

Abstract

Provided are 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. Also provided are methods for evaluating, identifying, assessing, and/or treating an individual having a colorectal cancer.

Description

BIOMARKERS FOR COLORECTAL CANCER TREATMENT

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority benefits of International Patent Applications No. PCT/CN2021/105822 filed July 12, 2021, and International Patent Applications No. PCT/CN2021/105816 filed July 12, 2021, the contents of each of which are incorporated herein by reference in their entirety.

FIELD

The present disclosure relates to biomarkers associated with colorectal cancers, as well as to methods of diagnosis, assessment, and treatment of colorectal cancers.

BACKGROUND

Colorectal cancer is the third most common cancer in the world, the second leading cause of cancer-related deaths, 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. At present, the treatment of early-stage colorectal cancer is usually carried out by surgery or radiotherapy. In addition to surgery and radiotherapy, middle-and late-stage patients are usually treated systematically in combination with chemotherapy and targeted drug therapies. With current treatments, the five-year survival rate for early-stage colorectal cancer exceeds 90%, while the five-year survival rate for advanced metastatic colorectal cancer is only 14%.

Some anti-cancer therapy, such as radiation and certain chemotherapeutic drugs, can cause double-stranded DNA breaks (DSBs) . Homologous recombination (HR) and non-homologous end-joining (NHEJ) are the two major pathways for repairing DSBs in eukaryotic cells. HR repairs DSBs by replicating from a stretch of homologous DNA, while NHEJ repairs DSBs by processing and re-ligating the DSB ends (Thompson, et al., 2001; Lieber, et al., 2004) . Unlike HR with high fidelity of DNA repairing, NHEJ is often error-prone, due to small deletions or extensive degradation at the DSB site prior to re-ligation, which usually introduces large-scale genomic recombination, leading to genetic instability and cell death.

Poly (ADP ribose) polymerase (PARP) is implicated in colorectal cancer. PAPR protein binds to DNA sites and catalyzes 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 repair DNA damage together. The PARP inhibitor (PARPi) binds to the PARP catalytic site, causing the PARP protein to fail to fall off the DNA damage site, leading to the stall of the DNA replication fork and failing to repair the DSB. By inhibiting the repair of tumor cell DNA damage, the PARP inhibitor promotes tumor cell apoptosis, and ultimately achieves a therapeutic effect. Although multiple PARP inhibitors have been developed as potential anti-cancer drugs, the effectiveness of these inhibitors have yet to be improved.

Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family of serine/threonine protein kinases. ATR kinase is a major regulator of DNA damage response and is activated by the extensive presence of single-stranded DNA structures (ssDNA) . Most ssDNAs arise from a stalled DNA replication stress or other types of DNA damage, including resected DNA DSB, crosslinks, base adduct, and inhibition of DNA polymerases. When DNA damage occurs, ATR functions primarily through the phosphorylation and activation of its downstream target CHK1, leading to stabilization of stalled replication forks, origin firing, activation of DNA damage repair and various checkpoints of the cell cycle. Despite of decades of knowledge on ATR and its great potential as an anti-cancer target, ATR inhibitor (ATRi) is yet to be clinically successful in cancer treatment (F.M. Barnieh et al. “Progress towards a clinically-successful ATR inhibitor for cancer therapy. ” Current Research in Pharmacology and Drug Discovery, 2021; Volume 2, 100017) .

BRIEF SUMMARY

The present application in one aspect provide a method of treating a colorectal cancer in an individual (e.g., 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 on the basis of having one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual. In some embodiments, there is provide a method of treating a colorectal cancer in an individual (e.g., 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 on the basis of having a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level in a sample from the individual; wherein the drug sensitive aberration (e.g., mutation) is one or more drug sensitive aberrations (e.g., mutations) in one or a plurality of drug sensitive 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 resistant aberration (e.g., mutation) is one or more drug resistant aberrations (e.g., mutations) in one or a plurality of drug resistant 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. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, there is provide a method of treating a colorectal cancer in an individual (e.g., 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 on the basis of having a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level in a sample from the individual; wherein the drug sensitive aberration (e.g., mutation) is one or more drug sensitive aberrations (e.g., mutations) in one or a plurality of drug sensitive 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 resistant aberration (e.g., mutation) is one or more drug resistant aberrations (e.g., mutations) in one or a plurality of drug resistant 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 composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., 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 on the basis of having one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual. In some embodiments, there is provide a method of treating a colorectal cancer in an individual (e.g., 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 on the basis of having a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level in a sample from the individual; wherein the drug sensitive aberration (e.g., mutation) is one or more drug sensitive aberrations (e.g., mutations) in one or a plurality of drug sensitive 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 wherein the drug resistant aberration (e.g., mutation) is one or more drug resistant aberrations (e.g., mutations) in one or a plurality of drug resistant 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 composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment on the basis of having one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment on the basis of having one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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, there is provide a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment on the basis of having a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level in a sample from the individual; wherein the drug sensitive aberration (e.g., mutation) is one or more drug sensitive aberrations (e.g., mutations) in one or a plurality of drug sensitive 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 resistant aberration (e.g., mutation) is one or more drug resistant aberrations (e.g., mutations) in one or a plurality of drug resistant 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, there is provide a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual is selected for treatment on the basis of having a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level in a sample from the individual; wherein the drug sensitive aberration (e.g., mutation) is one or more drug sensitive aberrations (e.g., mutations) in one or a plurality of drug sensitive 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 resistant aberration (e.g., mutation) is one or more drug resistant aberrations (e.g., mutations) in one or a plurality of drug resistant 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 composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of an ATRi, wherein the individual is selected for treatment on the basis of having one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual. In some embodiments, there is provide a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of an ATRi, wherein the individual is selected for treatment on the basis of having a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level in a sample from the individual; wherein the drug sensitive aberration (e.g., mutation) is one or more drug sensitive aberrations (e.g., mutations) in one or a plurality of drug sensitive 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 wherein the drug resistant aberration (e.g., mutation) is one or more drug resistant aberrations (e.g., mutations) in one or a plurality of drug resistant 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. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a PARP inhibitor. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of an ATRi. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of an ATRi. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample of the individual, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample of the individual, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample of the individual, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual, administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample of the individual, administering to the individual an effective amount of an PARP inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample of the individual, administering to the individual an effective amount of an PARP inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual, administering to the individual an effective amount of an PARP inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual, administering to the individual an effective amount of an PARP inhibitor. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample of the individual, administering to the individual an effective amount of an ATR inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample of the individual, administering to the individual an effective amount of an ATR inhibitor. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, the acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample of the individual comprises detecting the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in the sample.

In some embodiments, the acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual comprises detecting the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the sample.

In some embodiments, the acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual comprises detecting the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the sample.

In some embodiments, the acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual comprises detecting the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the sample. In some embodiments, the acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample of the individual comprises detecting the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the sample.

In some embodiments, the acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample of the individual comprises detecting the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in the sample.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, and administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) .

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) .

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) .

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and administering to the individual an effective amount of a PARP inhibitor. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, and administering to the individual an effective amount of a PARP inhibitor.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, and administering to the individual an effective amount of an ATR inhibitor.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) , wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) , wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 wherein a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) , wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) , wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARPi or ATRi) , wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of a PARP inhibitor, wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 wherein a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of an ATR inhibitor, wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual (e.g., human) , comprising administering to the individual an effective amount of an ATR inhibitor, wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, and wherein a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies the individual as one who may benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may not benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, wherein the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies the individual as one who may not benefit from a treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, wherein a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies the individual as one who may benefit from the treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies the individual as one who may benefit from the treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies the individual as one who may benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may not benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies the individual as one who may not benefit from a treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies the individual as one who may benefit from the treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a PARP inhibitor, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies the individual as one who may benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a PARP inhibitor, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies the individual as one who may benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may not benefit from a treatment comprising administration of a PARP inhibitor, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies the individual as one who may not benefit from a treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may not benefit from a treatment comprising administration of a PARP inhibitor, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies the individual as one who may not benefit from a treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a PARP inhibitor, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies the individual as one who may benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of a PARP inhibitor, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies the individual as one who may benefit from the treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of an ATR inhibitor, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies the individual as one who may benefit from the treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may not benefit from a treatment comprising administration of an ATR inhibitor, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies the individual as one who may not benefit from a treatment. In some embodiments, provided herein is a method of identifying an individual (e.g., human) having a colorectal cancer who may benefit from a treatment comprising administration of an ATR inhibitor, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies the individual as one who may benefit from the treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) as a suitable treatment for the individual. In some embodiments, provided herein is a method of selecting treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, wherein the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) as an unsuitable treatment for the individual. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, wherein a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) as a suitable treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) as a suitable treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) as a suitable treatment for the individual. In some embodiments, provided herein is a method of selecting treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) as an unsuitable treatment for the individual. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) as a suitable treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies a treatment comprising administration of a PARP inhibitor as a suitable treatment for the individual. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies a treatment comprising administration of a PARP inhibitor as a suitable treatment for the individual. In some embodiments, provided herein is a method of selecting treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies a treatment comprising administration of a PARP inhibitor as an unsuitable treatment for the individual. In some embodiments, provided herein is a method of selecting treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies a treatment comprising administration of a PARP inhibitor as an unsuitable treatment for the individual. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies a treatment comprising administration of a PARP inhibitor as a suitable treatment for the individual. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies a treatment comprising administration of a PARP inhibitor as a suitable treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies a treatment comprising administration of an ATR inhibitor as a suitable treatment for the individual. In some embodiments, provided herein is a method of selecting treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies a treatment comprising administration of an ATR inhibitor as an unsuitable treatment for the individual. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies a treatment comprising administration of an ATR inhibitor as a suitable treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 (b) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 (b) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options do not comprise a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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; (b) detecting in the sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) and the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the method further comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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; (b) detecting in the sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) and the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the method further comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options do not comprise a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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) detecting in the sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) and the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the method further comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 (b) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options do not comprise a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options do not comprise a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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; (b) detecting in the sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) and the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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; (b) detecting in the sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) and the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a PARP inhibitor. In some embodiments, the method further comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 (b) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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; and (b) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options do not comprise a treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method of identifying one or more treatment options for an individual (e.g., human) having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in the sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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; and (c) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) and the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of an ATR inhibitor. In some embodiments, the method further comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) ; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate not to receive a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) ; and/or (ii) the individual is identified as unlikely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) ; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) ; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) ; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate not to receive a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) ; and/or (ii) the individual is identified as unlikely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) ; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as likely to respond 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., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate not to receive a treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as unlikely to respond 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., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate not to receive a treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as unlikely to respond to a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a PARP inhibitor; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a PARP inhibitor. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of an ATR inhibitor; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method of excluding a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate not to receive a treatment comprising administration of an ATR inhibitor; and/or (ii) the individual is identified as unlikely to respond to a treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method of selecting a treatment for an individual (e.g., human) having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of an ATR inhibitor; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of an ATR inhibitor. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the DNA damaging agent (e.g., PARPi or ATRi) , as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the DNA damaging agent (e.g., PARPi or ATRi) , as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the DNA damaging agent (e.g., PARPi or ATRi) , as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the DNA damaging agent (e.g., PARPi or ATRi) , as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) , the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the DNA damaging agent (e.g., PARPi or ATRi) , as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a PARP inhibitor, the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the PARP inhibitor, as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a PARP inhibitor, the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the PARP inhibitor, as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a PARP inhibitor, the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the PARP inhibitor, as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of a PARP inhibitor, the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the PARP inhibitor, as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of an ATR inhibitor, the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the ATR inhibitor, as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, provided herein is a method of predicting survival of an individual (e.g., human) having a colorectal cancer treated with a treatment comprising administration of an ATR inhibitor, the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the ATR inhibitor, as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in the individual, wherein said information identifies the individual as being suitable for a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in the individual, wherein said information identifies the individual as being unsuitable for a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in the individual, and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in the individual, wherein said information (e.g., a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level) identifies the individual as being suitable for a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in the individual, and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the individual, wherein said information (e.g., a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level) identifies the individual as being suitable for a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the individual, wherein said information identifies the individual as being suitable for a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the individual, wherein said information identifies the individual as being unsuitable for a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the individual, and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the individual, wherein said information (e.g., a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level) identifies the individual as being suitable for a treatment comprising administration of a DNA damaging agent (e.g., PARPi or ATRi) . In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the individual, wherein said information identifies the individual as being suitable for a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the individual, wherein said information identifies the individual as being suitable for a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the individual, wherein said information identifies the individual as being unsuitable for a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the individual, wherein said information identifies the individual as being unsuitable for a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the individual, and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the individual, wherein said information (e.g., a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level) identifies the individual as being suitable for a treatment comprising administration of a PARP inhibitor. In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 the individual, and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the individual, wherein said information (e.g., a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level) identifies the individual as being suitable for a 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.

In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in the individual, wherein said information identifies the individual as being suitable for a treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in the individual, wherein said information identifies the individual as being unsuitable for a treatment comprising administration of an ATR inhibitor. In some embodiments, provided herein is a method of evaluating an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in the individual, and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in the individual, wherein said information (e.g., a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level) identifies the individual as being suitable for a treatment comprising administration of an ATR inhibitor. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have increased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug resistant aberrations (e.g., drug resistant mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have increased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug resistant aberrations (e.g., drug resistant mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have increased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug resistant aberrations (e.g., drug resistant mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have increased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug resistant aberrations (e.g., drug resistant mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have increased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug resistant aberrations (e.g., drug resistant mutations) . In some embodiments, provided herein is a method of screening an individual (e.g., human) having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, the colorectal cancer is any of advanced colon cancer, malignant colon cancer, metastatic colon cancer, stage I, II, III, or IV colon cancer, a colon cancer characterized with a genomic instability, a colon cancer characterized with an alteration of a pathway, a colon cancer classified under the colon cancer subtype (CCS) system as CCS1, CCS2, or CCS3, a colon cancer classified under colorectal cancer assigner (CRCA system) as stem-like, goblet-like, inflammatory, transit-amplifying, or enterocyte subtype, a colon cancer classified under the colon cancer molecular subtype (CCMS) system as C1, C2, C3, C4, C5, or C6 subtype, a colon cancer classified under the CRC intrinsic subtype (CRCIS) system as Type A, Type B, or Type C subtype, or a colon cancer classified under the colorectal cancer subtyping consortium (CRCSC) classification system as CMS1, CMS2, CMS3, or CMS4. 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 undergone a therapy (e.g., chemotherapy, radiation, surgery or immunomodulatory therapy) . In some embodiments, the individual does not respond to a previous therapy (e.g., chemotherapy, radiation, surgery or immunomodulatory therapy) .

In some embodiments, the treatment or the one or more treatment options further comprise an additional anti-cancer treatment. In some embodiments, the additional anti-cancer treatment comprises one or more of a small molecule inhibitor, an antibody, a cellular therapy, or a nucleic acid. In some embodiments, the cellular therapy is an adoptive therapy, a T cell-based therapy, a natural killer (NK) cell-based therapy, a chimeric antigen receptor (CAR) -T cell therapy, a recombinant T cell receptor (TCR) T cell therapy, or a dendritic cell (DC) -based therapy. In some embodiments, the nucleic acid comprises a double-stranded RNA (dsRNA) , a small interfering RNA (siRNA) , or a small hairpin RNA (shRNA) . In some embodiments, the additional anti-cancer treatment comprises one or more of a surgery, radiotherapy, chemotherapy, anti-angiogenic therapy, anti-DNA repair therapy, anti-inflammatory therapy, an anti-neoplastic agent, a chemotherapeutic agent, a growth inhibitory agent, an anti-angiogenic agent, or a cytotoxic agent.

In some embodiments, the sample from the individual comprises fluid, cells, or tissue. In some embodiments, the sample from the individual comprises a tumor biopsy or a circulating tumor cell. In some embodiments, the sample from the individual comprises one or more nucleic acids. In some embodiments, the sample from the individual comprises RNA (e.g., 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 (e.g., DNA, RNA) and/or one or more polypeptides obtained from an FFPE sample from the individual. In some embodiments, the one or more nucleic acids comprise mRNA and/or genomic DNA. In some embodiments, the sample is derived from a colorectal cancer tissue in the individual.

In some embodiments, the sample is selectively enriched for the certain types of polypeptides (e.g., polypeptides or portion thereof encoded by one or a plurality of drug sensitive genes and/or one or a plurality of drug resistant genes) prior to the aberration (e.g., mutation or expression or activity or modification) analysis. In some embodiments, the selectively enriching comprises: (a) combining a bait with the sample, thereby allowing the bait to bind to the one or more polypeptides in the sample and producing bait-polypeptide complexes; and (b) isolating the bait-polypeptide complexes to produce the enriched sample. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to the polypeptides (or portion thereof) encoded by the one or a plurality of drug sensitive 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug resistant 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. In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to the polypeptides (or portion thereof) encoded by the one or a plurality of drug sensitive 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug resistant 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug sensitive 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug resistant 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug sensitive 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug resistant 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug sensitive 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug resistant 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 bait comprises a capture polypeptide molecule configured to bind to the polypeptides (or portion thereof) encoded by the one or a plurality of drug sensitive 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 the polypeptides (or portion thereof) encoded by the one or a plurality of drug resistant 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. In some embodiments, the capture polypeptide molecule is a polypeptide. In some embodiments, the capture polypeptide molecule is an antibody an antibody fragment. In some embodiments, the bait is conjugated to an affinity reagent or to a detection reagent. In some embodiments, the affinity reagent is biotin. In some embodiments, the detection reagent is a fluorescent marker. In some embodiments, the methods further comprise performing protein-sequencing or mass spectrometry on the one or more polypeptides in the enriched sample.

In some embodiments, the sample is selectively enriched for the certain types of nucleic acids (e.g., nucleic acids comprising or encoded by one or a plurality of drug sensitive genes and/or one or a plurality of drug resistant genes) prior to the aberration (e.g., mutation or expression or activity) analysis. In some embodiments, the selectively enriching comprises: (a) combining a bait with the sample, thereby hybridizing the bait to the one or more nucleic acids in the sample and producing nucleic acid hybrids; and (b) isolating the nucleic acid hybrids to produce the enriched sample. In some embodiments, the bait comprises a capture nucleic acid molecule configured to hybridize to the one or a plurality of drug sensitive genes (or RNAs 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, 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 nucleic acid molecule configured to hybridize to the one or a plurality of drug sensitive genes (or RNAs 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, 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 a plurality of drug resistant genes (or RNAs encoded 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 the one or a plurality of drug sensitive genes (or RNAs encoded 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 a plurality of drug resistant genes (or RNAs encoded 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 the one or a plurality of drug sensitive genes (or RNAs 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 a plurality of drug resistant genes (or RNAs encoded 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 the one or a plurality of drug sensitive genes (or RNAs encoded 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 a plurality of drug resistant genes (or RNAs encoded 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, the bait comprises a capture nucleic acid molecule configured to hybridize to the one or a plurality of drug sensitive genes (or RNAs encoded 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, 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 capture nucleic acid molecule comprises between about 10 and about 30 nucleotides, between about 50 and about 1000 nucleotides, between about 100 and about 500 nucleotides, between about 100 and about 300 nucleotides, or between about 100 and 200 nucleotides. In some embodiments, the bait is conjugated to an affinity reagent or to a detection reagent. In some embodiments, the affinity reagent is an antibody, an antibody fragment, or biotin, or wherein the detection reagent is a fluorescent marker. In some embodiments, the capture nucleic acid molecule comprises a DNA, RNA, or mixed DNA/RNA molecule. In some embodiments, the selectively enriching comprises amplifying the one or more nucleic acids in the sample using a polymerase chain reaction (PCR) to produce the enriched sample. In some embodiments, the methods further comprise sequencing the one or more nucleic acid molecules, or a relevant portion thereof (e.g., a nucleic acid fragment known to contain a mutation) , in the enriched sample.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, 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, there is provided a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs encoded 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs encoded 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs encoded 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, 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, there is provided a kit comprising a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, 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, there is provided a kit comprising a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a kit comprising a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs encoded 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a kit comprising a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a kit comprising a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs encoded 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 a plurality of drug resistant genes (or RNAs encoded 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, there is provided a kit comprising a plurality of capture nucleic acid molecules (or a plurality of baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes (or RNAs encoded 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, 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 a plurality of drug resistant genes (or RNAs encoded 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, 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 capture nucleic acid molecule comprises between about 10 and about 30 nucleotides, between about 50 and about 1000 nucleotides, between about 100 and about 500 nucleotides, between about 100 and about 300 nucleotides, or between about 100 and 200 nucleotides. In some embodiments, the bait is conjugated to an affinity reagent or to a detection reagent. In some embodiments, the affinity reagent is an antibody, an antibody fragment, or biotin, or wherein the detection reagent is a fluorescent marker. In some embodiments, the capture nucleic acid molecule comprises a DNA, RNA, or mixed DNA/RNA molecule. In some embodiments, the selectively enriching comprises amplifying the one or more nucleic acids in the sample using a PCR to produce the enriched sample. In some embodiments, the methods further comprise sequencing the one or more nucleic acid molecules, or a relevant portion thereof (e.g., a nucleic acid fragment known to contain a mutation) , in the enriched sample.

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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual (e.g., human) having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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. In some embodiments, the sequence reads are obtained from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual (e.g., human) having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) detect, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual (e.g., human) having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) detect, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual (e.g., human) having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) detect, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual (e.g., human) having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) detect, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual (e.g., human) having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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; and (c) detect, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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. In some embodiments, the sequence reads are obtained from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 for performing 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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyzing the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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) detecting, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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. In some embodiments, the sequence reads are obtained from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 for performing 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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyzing the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 for performing 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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyzing the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 for performing 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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyzing the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 for performing 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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyzing the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

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 for performing 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 peptides, wherein the one or more nucleic acids or peptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyzing the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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; and (c) detecting, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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. In some embodiments, the sequence reads are obtained from DNA-seq. In some embodiments, the sequence reads are obtained from RNA-seq. In some embodiments, the sequence reads are obtained from protein-seq (e.g., mass spectrometry) .

In some embodiments, the one or more mutations comprise one or more of an insertion, deletion or substitution of one or more nucleotides, a genomic rearrangement, an alteration in a promoter, a gene fusion, or a copy number alteration. In some embodiments, the one or more mutations result in one or more of an insertion, deletion or substitution of one or more amino acid residues in a polypeptide encoded by a drug sensitive gene or a drug resistant gene.

In some embodiments, the plurality of sequence reads is 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 (e.g., mass spectrometry) . In some embodiments, the entire gene or gene product (e.g., RNA, polypeptide) is sequenced. In some embodiments, a relevant portion of a gene or gene product (e.g., RNA, polypeptide) is sequenced, such as a nucleic acid or polypeptide fragment known to contain a mutation or modification.

In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating a colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 is detected in a sample obtained from the individual. In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating a colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 are detected in a sample obtained from the individual, and wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating a colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 are detected in a sample obtained from the individual, and wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating a colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 is detected in a sample obtained from the individual. In some embodiments, provided herein is a DNA damaging agent (e.g., PARPi or ATRi) for use in a method of treating a colorectal cancer, wherein the method comprises administering the DNA damaging agent to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 are detected in a sample obtained from the individual, and wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a PARP inhibitor for use in a method of treating a colorectal cancer, wherein the method comprises administering the PARP inhibitor to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 is detected in a sample obtained from the individual. In some embodiments, provided herein is a PARP inhibitor for use in a method of treating a colorectal cancer, wherein the method comprises administering the PARP inhibitor to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 is detected in a sample obtained from the individual. In some embodiments, provided herein is a PARP inhibitor for use in a method of treating a colorectal cancer, wherein the method comprises administering the PARP inhibitor to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 are detected in a sample obtained from the individual, and wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, provided herein is a PARP inhibitor for use in a method of treating a colorectal cancer, wherein the method comprises administering the PARP inhibitor to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 are detected in a sample obtained from the individual, and wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I.In some embodiments, the threshold level is zero.

In some embodiments, provided herein is an ATRi for use in a method of treating a colorectal cancer, wherein the method comprises administering the ATRi to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 is detected in a sample obtained from the individual. In some embodiments, provided herein is an ATRi for use in a method of treating a colorectal cancer, wherein the method comprises administering the ATRi to an individual (e.g., human) having a colorectal cancer, wherein one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive 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 resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant 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 are detected in a sample obtained from the individual, and wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

It is to be understood that one, some, or all of the properties of the various embodiments described herein may be combined to form other embodiments of the present invention. These and other aspects of the invention will become apparent to one of skill in the art. These and other embodiments of the invention are further described by the detailed description that follows.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows an exemplary procedure for screening drug sensitive and/or drug resistant genes to anti-cancer drug.

FIG. 2 shows exemplary screening workflow for Cas9 ⁺ sgRNA ^iBAR cancer cell library.

FIG. 3 shows an exemplary target gene identification workflow for Cas9 ⁺ sgRNA ^iBAR cancer cell library.

FIG. 4 shows PARPi response curves of cancer cells with drug sensitive genes or drug resistant genes knock-out (KO) . Cancer cells without such KOs treated with PARPi served as control (WT) .

FIG. 5A shows loss-of-function (LOF) mutation probability of drug sensitive genes and drug resistant genes of PARPi (y-axis, 51 genes total) in 16 cancer samples. FIG. 5B shows composite score calculated using Formula I based on 51 genes for each cancer sample. FIG. 5C shows composite score, response to PARPi treatment, and therapeutic efficacy prediction based on composite score for each cancer sample.

DETAILED DESCRIPTION

The present disclosure is based, at least in part, on the discovery of certain biomarkers and their association with drug sensitivity or drug resistance to the treatment of a DNA damaging agent, such as a PARP inhibitor or an ATRi. Specifically, using a proprietary high throughput screening platform, the inventors have identified a group of genes (referred to as “drug sensitive genes” ) which, when mutated (e.g., inactivated) in a colorectal cancer cell, render the colorectal cancer cell more sensitive to treatment with a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) as compared to a colorectal cancer cell not having such mutation (s) . The inventors have also identified a group of genes (referred to as “drug resistant genes” ) which, when mutated (e.g., inactivated) in a colorectal cancer cells, render the colorectal cancer cell more resistant to treatment with a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) as compared to a colorectal cancer cell not having such mutations. Aberrations (e.g., mutations, aberrant expression, aberrant activity, and/or aberrant modification (e.g., post-translational modification) ) in these genes can be useful biomarkers for treating (or not treating) an individual having colorectal cancer with a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) . For example, patients carrying a mutation (e.g., inactivation) in a drug sensitive gene described herein, and/or with reduced or absent expression (e.g., mRNA or protein) of the drug sensitive gene compared to a healthy individual, and/or with reduced or abolished activity of the drug sensitive gene (e.g., RNA or protein activity, such as due to epigenetic or post-translational modification) compared to a healthy individual, are particularly suitable for treatment with the corresponding anti-cancer drug.

Accordingly, the present invention in some embodiments provides a method of treating a colorectal cancer by a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) , wherein the treatment is based on the presence or absence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) described herein. In other aspects, provided herein are methods of identifying one or more treatment options for an individual having a colorectal cancer based on the presence or absence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) described herein, wherein the treatment options comprises a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) . In other aspects, provided herein are methods of selecting treatment for an individual having a colorectal cancer based on the presence or absence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) described herein. In other aspects, provided herein are methods of predicting survival of an individual having a colorectal cancer treated with a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) based on the presence or absence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) described herein. In other aspects, provided herein are methods of identifying an individual having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) based on the presence or absence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) described herein.

In other aspects, provided herein are systems comprising one or more processors; and a non-transitory computer readable storage medium comprising one or more programs executable by the one or more processors for performing any one of the methods described herein.

Definitions

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 “amolecule” optionally includes a combination of two or more such molecules, and the like.

The term “or” is used herein to mean, and is used interchangeably with, the term “and/or” , unless context clearly indicates otherwise.

The terms “about” or “approximately” as used herein refer to the usual error range for the respective value readily known to the skilled person in this technical field, for example, an acceptable degree of error or deviation for the quantity measured given the nature or precision of the measurements. Reference to “about” or “approximately” a value or parameter herein includes (and describes) embodiments that are directed to that value or parameter per se.

As used herein, the term “configured to hybridize to” indicates that a nucleic acid molecule has a nucleotide sequence with sufficient length and sequence complementarity to the nucleotide sequence of a target nucleic acid to allow the nucleic acid molecule to hybridize to the target nucleic acid, e.g., with a T _m of at least 65℃ in an aqueous solution of 1× SCC (150 mM sodium chloride and 15 mM trisodium citrate) and 0.1%SDS. Other hybridization conditions may be used when hybridizing a nucleic acid molecule to a target nucleic acid molecule, for example in the context of a described method.

“Percent (%) sequence identity” with respect to a reference polypeptide or polynucleotide sequence is defined as the percentage of amino acid residues or nucleotides in a sequence that are identical to the amino acid residues or nucleotides in the reference polypeptide or polynucleotide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity.

An “individual” or “subject” is a mammal. Mammals include, but are not limited to, domesticated animals (e.g., cows, sheep, cats, dogs, and horses) , primates (e.g., humans and non-human primates such as monkeys) , rabbits, and rodents (e.g., mice and rats) . In certain embodiments, the individual or subject is a human. In some embodiments, the individual is human patient, e.g., a human patient having a cancer described herein.

As used herein, “treatment” or “treating” is an approach for obtaining beneficial or desired results including clinical results. For purposes of this invention, beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms resulting from the disease, diminishing the extent of the disease, stabilizing the disease (e.g., preventing or delaying the worsening of the disease) , preventing or delaying the spread (e.g., metastasis) of the disease, preventing or delaying the recurrence of the disease, delay or slowing the progression of the disease, ameliorating the disease state, providing a remission (partial or total) of the disease, decreasing the dose of one or more other medications required to treat the disease, delaying the progression of the disease, increasing the quality of life, and/or prolonging survival. Also encompassed by “treatment” is a reduction of a pathological consequence of a cancer. The methods of the invention contemplate any one or more of these aspects of treatment.

As used herein, “delaying” the development of a cancer means to defer, hinder, slow, retard, stabilize, and/or postpone development of the disease. This delay can be of varying lengths of time, depending on the history of the disease and/or individual being treated. As is evident to one skilled in the art, a sufficient or significant delay can, in effect, encompass prevention, in that the individual does not develop the disease. A method that “delays” development of a cancer is a method that reduces probability of disease development in a given time frame and/or reduces the extent of the disease in a given time frame, when compared to not using the method. Such comparisons are typically based on clinical studies, using a statistically significant number of subjects. Cancer development can be detectable using standard methods, including, but not limited to, computerized axial tomography (CAT Scan) , Magnetic Resonance Imaging (MRI) , abdominal ultrasound, clotting tests, arteriography, or biopsy. Development may also refer to cancer progression that may be initially undetectable and includes occurrence, recurrence, and onset.

The term “effective amount” used herein refers to an amount of a compound or composition sufficient to treat a specified disorder, condition or disease such as ameliorate, palliate, lessen, and/or delay one or more of its symptoms. For therapeutic use, beneficial or desired results include, e.g., decreasing one or more symptoms resulting from the disease (biochemical, histologic and/or behavioral) , including its complications and intermediate pathological phenotypes presenting during development of the disease, increasing the quality of life of those suffering from the disease, decreasing the dose of other medications required to treat the disease, enhancing effect of another medication, delaying the progression of the disease, and/or prolonging survival of patients. In reference to a cancer, an effective amount comprises an amount sufficient to cause a tumor tissue to shrink and/or to decrease the growth rate of the tumor tissue or to prevent or delay other unwanted cell proliferation in the tumor. In some embodiments, an effective amount is an amount sufficient to delay development of a cancer. In some embodiments, an effective amount is an amount sufficient to prevent or delay recurrence. An effective amount can be administered in one or more administrations. In the case of cancer, the effective amount of the drug or composition may: (i) reduce the number of tumor cells; (ii) reduce the tumor size; (iii) inhibit, retard, slow to some extent and preferably stop a tumor cell infiltration into peripheral organs; (iv) inhibit (i.e., slow to some extent and preferably stop) tumor metastasis; (v) inhibit tumor growth; (vi) prevent or delay occurrence and/or recurrence of tumor; and/or (vii) relieve to some extent one or more of the symptoms associated with the cancer.

“Likely to respond” or “responsiveness” as used herein refers to any kind of improvement or positive response either 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, increase or elongation of progression free survival, or increase or elongation of overall survival.

“Likely to” or “increased likelihood, ” as used herein, refer to an increased probability that an event, item, object, thing or person will occur. Thus, in one example, an individual that is likely to respond to treatment with an anti-cancer therapy, e.g., an anti-cancer therapy provided herein, alone or in combination, has an increased probability of responding to treatment with the anti-cancer therapy alone or in combination, relative to a reference individual or group of individuals. “Unlikely to” refers to a decreased probability that an event, item, object, thing or person will occur relative to a reference individual or group of individuals. Thus, an individual that is unlikely to respond to treatment with an anti-cancer therapy, e.g., an anti-cancer therapy provided herein, alone or in combination, has a decreased probability of responding to treatment with the anti-cancer therapy, alone or in combination, relative to a reference individual or group of individuals.

“Doubling time” or “population doubling time” (PDT) herein refers to the time it takes for a cell population to double in size. Cell doubling time = ln (2) / (growth rate) . Growth rate (gr) refers to the amount of doubling in one unit of time.

in which N (t) is the number of cells at time t, N (0) is the number of cells at time 0, t is time (usually in hours) . When a cell population is an exponentially growing population, i.e., every individual cell doubles with every cell cycle, the growth rate only depends on the length of the cell cycle,

“Sample, ” as used herein, refers to a biological sample obtained or derived from a source of interest, as described herein.

Methods of the Disclosure

The present application in some embodiments provides a method of identifying an individual having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) , the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes, wherein the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies the individual as one who may benefit from the treatment.

In some embodiments, provided herein is a method of identifying an individual having a colorectal cancer who may not benefit from a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) , the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes, wherein the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies the individual as one who may not benefit from a treatment.

In some embodiments, provided herein is a method of identifying an individual having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) , the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes, wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies the individual as one who may benefit from the treatment. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes, wherein the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample identifies a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) as a suitable treatment for the individual.

In some embodiments, provided herein is a method of selecting treatment for an individual having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes, wherein the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample identifies a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) as an unsuitable treatment for the individual.

In some embodiments, provided herein is a method of selecting a treatment for an individual having a colorectal cancer, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes, wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) above a threshold level identifies a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) as a suitable treatment for the individual. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes; and (b) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) .

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes; and (b) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options do not comprise a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) .

In some embodiments, provided herein is a method of identifying one or more treatment options for an individual having a colorectal cancer, the method comprising: (a) detecting in a sample from the individual one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes; (b) detecting in the sample from the individual one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes; and (c) generating a report, wherein the report comprises one or more treatment options identified for the individual based at least in part on the presence of the one or more drug sensitive aberrations (e.g., drug sensitive mutations) and the one or more drug resistant aberrations (e.g., drug resistant mutations) in the sample, wherein the one or more treatment options comprise a treatment comprising administration of a DNA damaging agent (e.g., a PARP inhibitor or an ATRi) . In some embodiments, the method further comprises obtaining a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of selecting a treatment for an individual having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) ; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) . In some embodiments, provided herein is a method of excluding a treatment for an individual having a colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate not to receive a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) ; and/or (ii) the individual is identified as unlikely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) . In some embodiments, provided herein is a method of selecting a treatment for an individual having a colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample from the individual, wherein responsive to the acquisition of knowledge: (i) the individual is classified as a candidate to receive a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) ; and/or (ii) the individual is identified as likely to respond to a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of predicting survival of an individual having a colorectal cancer treated with a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) , the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes in a sample from the individual, , wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the DNA damaging agent (e.g., PARP inhibitor or ATRi) , as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, provided herein is a method of predicting survival of an individual having a colorectal cancer treated with a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) , the method comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have longer survival after treatment with the DNA damaging agent (e.g., PARP inhibitor or ATRi) , as compared to an individual who does not have the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in an equivalent sample. In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of evaluating an individual having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes in the individual, wherein said information identifies the individual as being suitable for a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) . In some embodiments, provided herein is a method of evaluating an individual having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in the individual, wherein said information identifies the individual as being unsuitable for a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) . In some embodiments, provided herein is a method of evaluating an individual having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising: acquiring information that identifies one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive in the individual and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in the individual, wherein said information (e.g., a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level) identifies the individual as being suitable for a treatment comprising administration of a DNA damaging agent (e.g., PARP inhibitor or ATRi) . In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of screening an individual having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, provided herein is a method of screening an individual having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have increased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug resistant aberrations (e.g., drug resistant mutations) . In some embodiments, provided herein is a method of screening an individual having a colorectal cancer, suspected of having a colorectal cancer, being tested for a colorectal cancer, being treated for a colorectal cancer, or being tested for a susceptibility for colorectal cancer, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample from the individual, wherein responsive to the acquisition of said knowledge, the individual is predicted to have decreased risk of colorectal cancer recurrence, aggressive colorectal cancer, anti-cancer therapy resistance, or poor prognosis, as compared to an individual not having the one or more drug sensitive aberrations (e.g., drug sensitive mutations) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the method further comprises comparing the composite score with a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, there is provide a method of treating a colorectal cancer in an individual, comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, ATRi) , wherein the individual is selected for treatment on the basis of having one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes in a sample from the individual. In some embodiments, there is provide a method of treating a colorectal cancer in an individual, comprising administering to the individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, ATRi) , wherein the individual is selected for treatment on the basis of having a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) above a threshold level in a sample from the individual, wherein the drug sensitive aberrations (e.g., drug sensitive mutations) is one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and wherein the drug resistant aberrations (e.g., drug resistant mutations) is one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes in a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, or ATRi) . In some embodiments, provided herein is a method of treating a colorectal cancer in an individual, comprising acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample from the individual, and responsive to said knowledge, administering to the individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual, comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes in a sample of the individual, administering to the individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, or ATRi) . In some embodiments, provided herein is a method of treating a colorectal cancer in an individual, comprising responsive to acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample of the individual, administering to the individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, or ATRi) . In some embodiments, the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the sample of the individual. In some embodiments, the composite score of drug sensitive aberrations (e.g., drug sensitive mutations) and drug resistant aberrations (e.g., drug resistant mutations) in the individual is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments, the acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample of the individual comprises detecting the one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in the sample.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual, comprising detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample from the individual, and administering to the individual an effective amount of a DNA damaging agent, such as a PARP inhibitor, or an ATRi.

In some embodiments, provided herein is a method of treating a colorectal cancer in an individual, comprising administering to an individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, or ATRi) , wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes. In some embodiments, provided herein is a method of treating a colorectal cancer in an individual, comprising administering to an individual an effective amount of a DNA damaging agent (e.g., PARP inhibitor, or ATRi) , wherein the individual comprises one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes, and wherein a composite score of the drug sensitive aberrations (e.g., drug sensitive mutations) and the drug resistant aberrations (e.g., drug resistant mutations) is above a threshold level. In some embodiments, the composite score is determined by Formula I. In some embodiments, the threshold level is zero.

In some embodiments according to any of the methods described above that utilize information about drug sensitive genes, the one or a plurality of drug sensitive genes is selected from the group consisting of drug sensitive genes provided in Table 1, or is selected from the group consisting of drug sensitive genes provided in Table 2. In some embodiments, the one or a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, or all genes provided in Table 1 or Table 2.

Table 1. Drug sensitive genes of DNA damaging agent (s)

Table 2. Drug sensitive genes of DNA damaging agent (s)

In some embodiments according to any of the methods described above that utilize information about drug sensitive genes, the one or a plurality of drug sensitive genes is selected from the group consisting of drug sensitive genes provided in Table 3 . In some embodiments, the one or a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, or all genes provided in Table 3 . In some embodiments according to any of the methods described above that utilize information about drug sensitive genes, the one or a plurality of drug sensitive genes is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, or all genes provided in Table 3a) . In some embodiments, the one or a plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20 or all genes provided in Table 3b) . In some embodiment, the one or plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, or all genes provided in Table 3c) . In some embodiment, the one or plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, or all genes provided in Table 3d) . In some embodiment, the one or plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85 , 90 or all genes provided in Table 3e) . In some embodiments, the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table A.

Table 3. Drug sensitive genes of PARPi

Table A. Drug sensitive genes of PARPi

In some embodiments according to any of the methods described above that utilize information about drug sensitive genes, the one or a plurality of drug sensitive genes is selected from the group consisting of drug sensitive genes provided in Table 4. In some embodiments, the one or a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, or all genes provided in Table 4. In some embodiments according to any of the methods described above that utilize information about drug sensitive genes, the one or a plurality of drug sensitive genes is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 4a) . In some embodiments, the one or a plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 4b) . In some embodiment, the one or plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 4c) . In some embodiment, the one or plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 4d) . In some embodiment, the one or plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, or all genes provided in Table 4e) . In some embodiment, the one or plurality of drug sensitive gene is 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 a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, or all genes provided in Table 4f) .

Table 4. Drug sensitive genes of ATRi

In some embodiments according to any of the methods described above that utilize information about drug resistant genes, the one or a plurality of drug resistant genes is selected from the group consisting of drug resistant genes provided in Table 5, or is selected from the group consisting of drug resistant genes provided in Table 6. In some embodiments, the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, or all genes provided in Table 5 or Table 6.

Table 5. Drug resistant genes of DNA damaging agent (s)

Table 6. Drug resistant genes of DNA damaging agent (s)

In some embodiments according to any of the methods described above that utilize information about drug resistant genes, the one or a plurality of drug resistant genes is selected from the group consisting of drug resistant genes provided in Table 7. In some embodiments, the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, or all genes provided in Table 7. In some embodiments according to any of the methods described above that utilize information about drug resistant genes, the one or a plurality of drug resistant genes is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 7a) . In some embodiments, the one or a plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 7b) . In some embodiment, the one or plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, or all genes provided in Table 7c) . In some embodiment, the one or plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 7d) . In some embodiment, the one or plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, or all genes provided in Table 7e) . In some embodiments, the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, or all genes provided in Table B.

Table 7. Drug resistant genes of PARPi

Table B. Drug resistant genes of PARPi

In some embodiments according to any of the methods described above that utilize information about drug resistant genes, the one or a plurality of drug resistant genes is selected from the group consisting of drug resistant genes provided in Table 8. In some embodiments, the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, or all genes provided in Table 8. In some embodiments according to any of the methods described above that utilize information about drug resistant genes, the one or a plurality of drug resistant genes is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, or all genes provided in Table 8a) . In some embodiments, the one or a plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, or all genes provided in Table 8b) . In some embodiment, the one or plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 8c) . In some embodiment, the one or plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, or all genes provided in Table 8d) . In some embodiment, the one or plurality of drug resistant gene is 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 a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 20, 30, 40, 50, 100, or all genes provided in Table 8e) .

Table 8. Drug resistant genes of ATRi

In some embodiments according to any of the methods described herein that utilize information about drug sensitive genes and drug resistant genes, the one or a plurality of drug sensitive genes is selected from the group consisting of drug sensitive genes provide in Table 1, and the one or a plurality of drug resistant genes is selected from the group consisting of drug resistant genes provided in Table 5. In some embodiments, the one or a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, or all genes provided in Table 1, and/or the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, or all genes provided in Table 5. In some embodiments according to any of the methods described herein that utilize information about drug sensitive genes and drug resistant genes, the one or a plurality of drug sensitive genes is selected from the group consisting of drug sensitive genes provide in Table 1, and the one or a plurality of drug resistant genes is selected from the group consisting of drug resistant genes provided in Table 6. In some embodiments, the one or a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 20, or all genes provided in Table 1, and/or the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, or all genes provided in Table 6. In some embodiments according to any of the methods described herein that utilize information about drug sensitive genes and drug resistant genes, the one or a plurality of drug sensitive genes is selected from the group consisting of drug sensitive genes provide in Table 2, and the one or a plurality of drug resistant genes is selected from the group consisting of drug resistant genes provided in Table 6. In some embodiments, the one or a plurality of drug sensitive genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, or all genes provided in Table 2, and/or the one or a plurality of drug resistant genes comprise at least about any of 1, 2, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100, 150, 200, or all genes provided in Table 6.

Aberrations

An “aberration” at a gene (e.g., target gene, drug sensitive gene, drug resistant gene) refers to a genetic and/or epigenetic aberration of a gene, an aberrant expression level, and/or an aberrant activity level, and/or an aberrant modification level of the gene (or gene product, such as RNA or protein) that may lead to abnormal loss of function or reduced function and/or abnormal expression (e.g., reduced or absent) of the RNA and/or protein encoded by the gene. In some embodiments, a genetic aberration comprises a change to the nucleic acid (such as DNA or RNA) or protein sequence (i.e. mutation) or an aberrant epigenetic feature associated with the gene, including, but not limited to, coding, non-coding, regulatory, enhancer, silencer, promoter, intron, exon, and untranslated regions of the gene. In some embodiments, an aberration at a gene comprises a mutation of the gene, includes, but not limited to, deletion, frameshift, insertion, indel, missense mutation, nonsense mutation, point mutation, silent mutation, splice site mutation, splice variant, and translocation. In some embodiments, the mutation may be a loss or deletion of the gene. In some embodiments, the mutation is a deleterious mutation. In some embodiments, an aberration at a gene comprises aberrant (e.g., reduced or absent) expression (e.g., mRNA or protein) of a gene compared to a control level. In some embodiments, an aberration at a gene comprises aberrant (e.g., reduced or abolished) activity of a gene product (e.g., RNA or protein) compared to a control level, such as activation or inhibition of downstream targets. In some embodiments, an aberration at a gene comprises aberrant modification (e.g., increased, decreased, or mis-modification) of a gene (e.g., at DNA level or histone level) or gene product (e.g., RNA or protein) compared to a control level, such as post-translational modification (e.g., phosphorylation, ubiquitination) . In some embodiments, an aberration at a gene comprises a copy number variation of the gene. In some embodiments, the copy number variation of the gene is caused by structural rearrangement of the genome, including deletions, duplications, inversion, and translocations. In some embodiments, an aberration at a gene comprises an aberrant epigenetic feature of the gene, including, but not limited to, DNA methylation, hydroxymethylation, increased or decreased histone binding, histone methylation, histone acetylation, chromatin remodeling, and the like. In some embodiments, the aberration is determined in comparison to a control or reference, such as a reference sequence (such as a nucleic acid sequence or a protein sequence) , a control expression (such as RNA or protein expression) level, a control activity (such as activation or inhibition of downstream targets) level, or a control modification (e.g., post-translational modification or epigenetic modification) level. In some embodiments, the aberrant expression level or the aberrant activity level in a gene may be below the control level (such as about any of 10%, 20%, 30%, 40%, 60%, 70%, 80%, 90%or more below the control level) . In some embodiments, the aberrant modification level in a gene (e.g., modification of DNA, nucleosome, RNA, or protein) may be below the control level (such as about any of 10%, 20%, 30%, 40%, 60%, 70%, 80%, 90%or more below the control level) , or above the control level (such as about any of 10%, 20%, 30%, 40%, 60%, 70%, 80%, 90%or more above the control level) . In some embodiments, the aberrant modification in a gene is a mis-modification, e.g., ubiquitination instead of phosphorylation. In some embodiments, the control level (e.g. expression level or activity level or modification level) is the median level (e.g. 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 that does not have the cancer, and optionally with comparable demographic characteristics (e.g. gender, age, ethnicity, etc. ) as the individual being/to be treated. In some embodiments, the control level (e.g. expression level or activity level or modification level) is a level (e.g. expression level or activity level or modification level) of a healthy tissue from the same individual. An aberration at a gene may be determined by comparing to a reference sequence, including epigenetic patterns of the reference sequence in a control sample. In some embodiments, the reference sequence is the sequence (DNA, RNA or protein sequence) corresponding to a fully functional allele of the corresponding gene, such as an allele (e.g. the prevalent allele) of the corresponding gene present in a healthy population of individuals that do not have the cancer, but may optionally have similar demographic characteristics (such as gender, age, ethnicity etc. ) as the individual being/to be treated.

An aberration at a target gene is herein also referred to as “target gene aberration, ” including but not limited to target gene mutation. An aberration at a drug sensitive gene is herein also referred to as “drug sensitive aberration, ” including but not limited to drug sensitive mutation, which makes the cancer cells sensitive to an anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) . An aberration at a drug resistant gene is herein also referred to as “drug resistant aberration, ” including but not limited to drug resistant mutation, which makes the cancer cells resistant to an anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) . An aberration at a patient gene is herein also referred to as “patient gene aberration, ” including but not limited to patient gene mutation. An aberration at a patient target gene is herein also referred to as “patient target gene aberration, ” including but not limited to patient target gene mutation.

The “status” of an aberration at a gene may refer to the presence or absence of the aberration at the gene, or the aberrant level (expression or activity or modification level) of the gene. In some embodiments, the presence of an aberration (such as a mutation) in one or more drug sensitive genes as compared to a control indicates that (a) the individual is more likely to respond to an anti-cancer drug treatment or (b) the individual is selected for an anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) treatment. In some embodiments, the absence of an aberration (such as a mutation) in one or more drug sensitive genes compared to a control, indicates that (a) the individual is less likely to respond to an anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) treatment or (b) the individual is not selected for an anti-cancer drug treatment. In some embodiments, an aberrant level (such as expression level or activity level or modification level) of one or more drug sensitive genes and/or one or more drug resistant genes is correlated with the likelihood of the individual to respond to treatment. For example, a larger deviation of the level (e.g. expression or activity or modification level) of one or more drug sensitive genes in the direction of reducing or abolishing the gene function indicates that the individual is more likely to respond to an anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) treatment. In some embodiments, a prediction model (e.g., composite score) based on the level (s) (e.g. expression level or activity level or modification level) of one or more drug sensitive genes and/or one or more drug resistant genes is used to predict (a) the likelihood of the individual to respond to an anti-cancer drug treatment and (b) whether to select the individual for an anti-cancer drug treatment. In some embodiments, the prediction model, including, for example, coefficient for each level, may be obtained by statistical analysis, such as regression analysis, using clinical trial data.

In some embodiments, detecting the one or more drug sensitive aberrations and/or drug resistant aberrations comprises detecting mutation (s) in the one or more drug sensitive genes and/or the one or more drug resistant genes (or gene product) , such as by DNA-seq, RNA-seq, mass spectrometry, or any other nucleic acid/peptide sequence detection methods. In some embodiments, detecting the one or more drug sensitive aberrations and/or drug resistant aberrations comprises detecting aberrant (e.g., reduced or absent) expression (e.g., RNA or protein) of the one or more drug sensitive genes and/or the one or more drug resistant genes compared to a control level, such as by qPCR, RNA-seq, mass spectrometry, western blot, or any other RNA or protein expression level detection methods. In some embodiments, detecting the one or more drug sensitive aberrations and/or drug resistant aberrations comprises detecting aberrant modification at the one or more drug sensitive genes and/or the one or more drug resistant genes compared to a control level (e.g., healthy individual) , such as epigenetic modification (e.g., DNA methylation, histone methylation, histone acetylation) or post-translational modification (e.g., ubiquitination, phosphorylation) . Any known methods for detecting modification (s) on DNA, nucleosome, RNA, or protein can be used herein, such as ChIP-seq, ChIP-qPCR, DNase-seq, MNase-seq, mass spectrometry, western blot, etc. In some embodiments, detecting the one or more drug sensitive aberrations and/or drug resistant aberrations comprises detecting aberrant (e.g., reduced or absent) activity of expression product (e.g., RNA or protein) (or portion thereof) of the one or more drug sensitive genes and/or the one or more drug resistant genes compared to a control level (e.g., healthy individual) . Any suitable gene function/activity testing methods can be used herein, such as detecting signal transduction, activation status (e.g., phosphorylation status) of downstream pathway molecules, protein-protein binding affinity and/or specificity, metabolism, cell behavior (e.g., cell proliferation, death, cell cycle) , cytokine release, etc.

Composite Score

In some embodiments, the composite score can be calculated, and/or the composite score threshold level can be selected, using any methods known in the art. For example, see response score or recombination proficiency score (RPS) in US20160369353, also see US20200254259, US20180068083, the contents of each of which are incorporated herein by reference in their entirety.

In some embodiments, the composite score is based on one or more of drug sensitive aberrations and/or drug resistant aberrations, such as one or more of drug sensitive mutations, drug resistant mutations, aberrant expression of the drug sensitive genes, aberrant expression of the drug resistant genes, aberrant activity of expression products of the drug sensitive genes, aberrant activity of expression products of the drug resistant genes, aberrant modification of the drug sensitive genes (or gene product) , and aberrant modification of the drug resistant genes (or gene product) , etc. In some embodiments, the composite score is obtained by subtracting (the number of drug resistant genes with drug resistant aberrations carried by the patient) from (the number of drug sensitive genes with drug sensitive aberrations carried by the patient) , wherein the individual is selected for treatment if the composite score is above zero. In some embodiments, the severity of the drug sensitive mutation or drug resistant mutation in the patient adds weight to the composite score, for example, a drug sensitive mutation that affects the expression and/or activity of a drug sensitive gene more adds more weight to the composite score compared to another drug sensitive mutation that affects less of the expression and/or activity of the same drug sensitive gene. In some embodiments, the degree of the aberrant expression of a drug sensitive gene or a drug resistant gene in the patient compared to a control level (e.g., healthy individual) adds weight to the composite score, for example, loss of expression of a drug sensitive gene adds more weight to the composite score compared to reduced expression of the same drug sensitive gene. In some embodiments, the degree of the aberrant activity (e.g., RNA or protein activity) of a drug sensitive gene or a drug resistant gene in the patient compared to a control level (e.g., healthy individual) adds weight to the composite score, for example, loss of protein activity (e.g., abolished binding) of a drug sensitive gene adds more weight to the composite score compared to reduced protein activity (e.g., reduced binding) of the same drug sensitive gene. In some embodiments, the degree of the aberrant modification (e.g., modification of DNA, nucleosome, RNA, or protein) of a drug sensitive gene or a drug resistant gene in the patient compared to a control level (e.g., healthy individual) adds weight to the composite score, for example, loss of protein phosphorylation of a drug sensitive gene (e.g., abolishes signal transduction) adds more weight to the composite score compared to reduced protein phosphorylation of the same drug sensitive gene. In some embodiments, each drug resistant gene has a resistance score, and each drug sensitive gene has a sensitivity score (e.g., 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 resistant genes) from (the absolute value of the sum of the sensitivity scores of the drug sensitive genes) , wherein the individual is selected for treatment if the composite score is above zero.

In some embodiments, for a particular cancer type (e.g., colorectal cancer) and/or a particular anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) , parameter “m” is the total number of drug resistant genes and drug sensitive genes described herein (hereinafter also referred to as “gene panel described herein” ) . For example, in some embodiments, for a DNA damaging agent for treating a colorectal cancer, parameter “m” is the total number of drug sensitive genes provided in Table 1 and drug resistant genes provided in Table 5 ( “gene panel 1” ) . In some embodiments, for a DNA damaging agent for treating a colorectal cancer, parameter “m” is the total number of drug sensitive genes provided in Table 1 and drug resistant genes provided in Table 6 ( “gene panel 2” ) . In some embodiments, for a DNA damaging agent for treating a colorectal cancer, parameter “m” is the total number of drug sensitive genes provided in Table 2 and drug resistant genes provided in Table 6 ( “gene panel 3” ) . In some embodiments, for a PARPi for treating a colorectal cancer, parameter “m” is the total number of drug sensitive genes provided in Table 3 and drug resistant genes provided in Table 7 ( “gene panel 4” ) . In some embodiments, for an ATRi for treating a colorectal cancer, parameter “m” is the total number of drug sensitive genes provided in Table 4 and drug resistant genes provided in Table 8 ( “gene panel 5” ) . In some embodiments, for a PARPi for treating a colorectal cancer, parameter “m” is the total number of drug sensitive genes provided in Table A and drug resistant genes provided in Table B ( “gene panel 6” ) . In some embodiments, from a sample of an individual, one or more patient aberrations (e.g., mutation, or aberrant expression/activity/modification) , such as one or more patient mutations (e.g., nonsynonymous, nonsense, missense, frameshift, insertion, deletion, stop-loss, stop-gain, mutation that results in mis-splicing, gene fusion, etc. ) , are identified in one or more patient genes that belong to the gene panel described herein, or belong to gene panel 1, or gene panel 2, or gene panel 3, or gene panel 4, or gene panel 5, or gene panel 6. In some embodiments, from a sample of an individual, no patient aberration (e.g., patient mutation) is identified in a patient gene that belong to the gene panel described herein, or belong to gene panel 1, or gene panel 2, or gene panel 3, or gene panel 4, or gene panel 5, or gene panel 6. Patient gene (s) or patient aberrations (e.g., mutation, or aberrant expression/activity/modification) identified from a patient (e.g., patient sample, such as by NGS) that belong to the gene panel described herein, or belong to gene panel 1, or gene panel 2, or gene panel 3, or gene panel 4, or gene panel 5, or gene panel 6, are hereinafter also referred to as “patient target gene (s) ” or “patient target aberration (s) ” (such as “patient target mutation (s) ” ) , respectively. Parameter “m” is an integer of at least 1, and is a constant for specific cancer type and specific anti-cancer drug.

In some embodiments, the composite score is calculated based on one or more patient-related parameters, such as i) the number of deleterious mutation (s) (e.g., nonsynonymous, nonsense, missense, frameshift, insertion, deletion, stop-loss, stop-gain, mutation that results in mis-splicing, gene fusion, etc. ) carried on each patient target gene identified (e.g., via NGS) from the patient (parameter “n” ) , ii) the estimated fraction of cells carrying a specific deleterious mutation in a specific patient target gene identified (e.g., via NGS) from the patient (parameter

) , iii) the log-scale (e.g., log2) fold change of expression level of a patient target gene in patient disease tissue vs. normal tissue (parameter “LFC” ) , etc. In some embodiments, the one or more patient-related parameters are derived based on data/information from patient sample, such as sequencing read counts. Parameter

denotes estimated fraction of cells carrying j ^th mutation in i ^th patient target gene identified from the patient.

“n” is an integer of at least 1, and is the total number of detected deleterious patient target mutations of the corresponding identified patient target gene. “j” is an integer, and 1 ≤ j ≤ n. “i” is an integer, and 0 ≤ i ≤ m. When i = 0, it indicates that from the sample of the individual, no deleterious mutation is identified in any patient gene that belongs to the gene panel described herein, or belong to gene panel 1, or gene panel 2, or gene panel 3, or gene panel 4, or gene panel 5, or gene panel 6. In some embodiments, the fraction of cells carrying j ^th mutation in i ^th patient target gene is estimated based on the fraction of sequences comprising the j ^th mutation among all sequences comprising a mutation in the i ^th patient target gene identified from the patient sample. Parameter “LFC _i” denotes the log-scale (e.g., log2) fold change of expression level of i ^th patient target gene in patient disease tissue vs. normal tissue. Expression level of a patient target gene can be measured using any known methods, such as RNA-seq, qPCR, mass spectrometry, western blot, FISH, immunofluorescence staining, etc.

In some embodiments, the composite score is calculated based on one or more gene-related parameters, such as i) the correlation (positive correlation or negative correlation) between a patient target gene and an anti-cancer drug treatment (e.g., at IC50) (parameter “r” ) , which is derived from machine learning (e.g., based on training models from public data on cell lines) , ii) the normalized weight of a patient target gene in response to an anti-cancer drug treatment (parameter

) , which is derived from machine learning (e.g., based on training models from public data on cell lines) , iii) the predicted impact of a deleterious mutation of a patient target gene (parameter “η” ; e.g., based on harmfulness prediction with public databases, such as aberrant gene or gene product activity) , iv) the ratio of net survival contribution of a patient target gene to total survival at a given time point according to the Kaplan-Meier survival curve (parameter

e.g., based on The Cancer Genome Atlas (TCGA) database and/or cBioPortal database) , v) the log-scale (e.g., log2) fold change of expression level of a patient target gene in disease tissue vs. normal tissue (parameter “LFC” ; e.g., based on patient database (s) , i.e., information collected from patients having the same cancer) , etc. In some embodiments, the one or more gene-related parameters are derived based on data in public or patient database (s) , for training the composite score model. Parameter “r _i” denotes the correlation (positive correlation or negative correlation) between i ^th patient target gene identified from the patient and an anti-cancer drug treatment (e.g., at IC50) , which is derived from machine learning. Parameter

denotes the normalized weight of i ^th patient target gene in response to an anti-cancer drug treatment (i.e., the contribution of the loss-of-function of i ^th patient target gene to the anti-cancer drug treatment) , which is derived from machine learning. Parameter “η _ij” denotes the predicted impact of the j ^th deleterious mutation of i ^th patient target gene (e.g., based on harmfulness prediction with public databases, or is a manually assigned constant) . Parameter

denotes the ratio of net survival contribution of i ^th patient target gene to total survival at a given time point according to the Kaplan-Meier survival curve (e.g., based on TCGA and/or cBioPortal databases) . Parameter “LFC _i” denotes the log-scale (e.g., log2) fold change of expression level of i ^th patient target gene in disease tissue vs. normal tissue (e.g., based on patient database (s) , i.e., information collected from patients having the same cancer) . “i” is an integer, and 0 ≤ i ≤ m. “j” is an integer, and 1 ≤ j ≤ n.

In some embodiments, the composite score is calculated based on one or more pathway-related parameters, such as i) the estimated weight of a patient target gene in pathway (s) and/or regulatory network (s) involving the patient target gene (parameter

e.g., based on public database (s) such as KEGG and InterProScan) , ii) the normalized weight of a patient target gene in anti-cancer drug-related pathway (s) (parameter “ψ” ; e.g., based on public database (s) ) , etc. In some embodiments, the one or more pathway-related parameters are derived based on data in public database (s) , for training the composite score model. Parameter

denotes the estimated weight of i ^th patient target gene in pathway (s) and/or regulatory network (s) involving i ^th patient target gene (e.g., based on public database (s) such as KEGG and InterProScan) . Parameter “ψ _i” denotes the normalized weight of i ^th patient target gene in anti-cancer drug-related pathway (s) , e.g., based on public database (s) . “i” is an integer, and 0 ≤ i ≤ m.

In some embodiments, the composite score is calculated based on one or more parameters selected from one or more of patient-related parameters, gene-related parameters, and pathway-related parameters described herein.

In some embodiments, the composite score is calculated using Formula I:

wherein

a, b, and c are constants for model tuning (e.g., constants derived from trained model for corresponding anti-cancer drug) , wherein -1 ≤ a ≤ 1, -1 ≤ b ≤ 1, and -1 ≤ c ≤ 1;

m is the total number of drug resistant genes and drug sensitive genes in the gene panel described herein (e.g., any of gene panels 1-6) ;

n is the number of deleterious mutation (s) detected on i ^th patient target gene in the patient;

is the estimated fraction of patient cells carrying j ^th deleterious mutation in i ^th patient target gene, wherein

r _i is the correlation (positive correlation or negative correlation) between i ^th patient target gene and the anti-cancer drug treatment (e.g., at IC50) ;

is the normalized weight of i ^th patient target gene in response to the anti-cancer drug treatment;

η _ij is the predicted impact of the j ^th deleterious mutation of i ^th patient target gene;

is the ratio of net survival contribution of i ^th patient target gene to total survival at a given time point according to the Kaplan-Meier survival curve;

LFC _i is the log-scale (e.g., log2) fold change of expression level of i ^th patient target gene in disease tissue vs. normal tissue;

is the estimated weight of i ^th patient target gene in pathway (s) and/or regulatory network (s) involving i ^th patient target gene;

ψ _i is the normalized weight of i ^th patient target gene in the anti-cancer drug-related pathway (s) ; wherein i and j are both integers, 0 ≤ i ≤ m, and 1 ≤ j ≤ n; and

Z (LFC _i) is the standard score ( “Z-score” ) of LFC _i:

wherein

is the median log-scale (e.g., log2) fold change of expression level of i ^th patient target gene in disease tissue vs. normal tissue (e.g., based on patient databases, i.e., information collected from patients having the same cancer) ; and

wherein σ _i is the standard deviation of log-scale (e.g., log2) fold change of expression level of i ^th patient target gene in disease tissue vs. normal tissue (e.g., based on patient databases, i.e., information collected from patients having the same cancer) .

In some embodiments, the composite score threshold level is 0. In some embodiments, if the composite score of the patient according to Formula I is above 0, the patient is suitable for (i.e., may benefit from) the anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) treatment. In some embodiments, if the composite score of the patient according to Formula I is above or equal to at least 0.1 (e.g., 0.3) , the patient is selected for or is recommended for the anti-cancer drug treatment. In some embodiments, if the composite score of the patient according to Formula I is more than 0 but less than 0.1, the patient is suitable for the anti-cancer drug treatment, but should be further evaluated using other method (s) (e.g., drug dosage test, cancer genetic testing (e.g., look for additional synergistic mutations that may contribute to the anti-cancer drug treatment, or verify the primary cancer type) , etc. ) or based on other information (e.g., patient’s clinical record or known drug resistance, etc. ) to determine whether the patient should be selected or recommended for the anti-cancer drug treatment. In some embodiments, if the composite score of the patient according to Formula I is below or equal to 0, the patient is not suitable for (i.e., may not benefit from) or is excluded from the anti-cancer drug treatment. In some embodiments, further evaluation using other method (s) (e.g., drug dosage test, cancer genetic testing (e.g., look for additional synergistic mutations that may contribute to the anti-cancer drug treatment, or verify the primary cancer type) , etc. ) or based on other information (e.g., patient’s clinical record or known drug resistance, etc. ) should be conducted if the composite score of the patient according to Formula I is equal to 0, or very close to 0 (e.g., -0.1 to 0) , before completely ruling out the patient from receiving the anti-cancer drug treatment.

In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug resistant genes (or portion thereof) , such as a drug resistant 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, 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, 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 a plurality of drug resistant genes (or portion thereof) , such as a drug resistant 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, 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein.

In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, 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 a plurality of drug resistant genes (or portion thereof) , such as a drug resistant 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein.

In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug resistant genes (or portion thereof) , such as a drug resistant 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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 a plurality of drug resistant genes (or portion thereof) , such as a drug resistant 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein.

In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug resistant genes (or portion thereof) , such as a drug resistant 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, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug resistant genes (or portion thereof) , such as a drug resistant gene 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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 a plurality of drug resistant genes (or portion thereof) , such as a drug resistant 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, Kras, CDKN2A, CHEK1, PKMYT1, SIDT2, and FGF19, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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 a plurality of drug resistant genes (or portion thereof) , such as a drug resistant gene 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein.

In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug resistant genes (or portion thereof) , such as a drug resistant gene 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein. In some embodiments, the methods further comprise selectively enriching in a sample in the individual one or more nucleic acids or polypeptides comprising or encoded by one or a plurality of drug sensitive genes (or portion thereof) , such as a drug sensitive 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, 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 a plurality of drug resistant genes (or portion thereof) , such as a drug resistant gene 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, to produce an enriched sample, e.g., using a reagent known in the art or provided herein, such as a bait, probe, capture molecule, or oligonucleotide described herein.

In some embodiments, the selectively enriching comprises: (a) combining a bait with the sample, thereby hybridizing the bait to the one or more nucleic acids in the sample and producing nucleic acid hybrids; and (b) isolating the nucleic acid hybrids to produce the enriched sample. In some embodiments, the selectively enriching comprises amplifying the one or more nucleic acids in the sample using a PCR to produce the enriched sample. In some embodiments, the methods further comprise sequencing the one or more nucleic acid molecules, or a relevant portion thereof (e.g., a nucleic acid fragment known to contain a mutation) , in the enriched sample. In some embodiments, the selectively enriching comprises: (a) combining a bait (e.g., antibody) with the sample, thereby binding the bait to the one or more polypeptides in the sample and producing bait-polypeptide complexes; and (b) isolating the bait-polypeptide complexes to produce the enriched sample.

Colorectal cancer

The methods described herein in some embodiments comprise treatment of colorectal cancer, also referred to as colon cancer, which include, but is not limited to, advanced colon cancer, malignant colon cancer, metastatic colon cancer, stage I, II, III, or IV colon cancer, a colon cancer characterized with a genomic instability, a colon cancer characterized with an alteration of a pathway, a colon cancer classified under the colon cancer subtype (CCS) system as CCS1, CCS2, or CCS3, a colon cancer classified under colorectal cancer assigner (CRCA system) as stem-like, goblet-like, inflammatory, transit-amplifying, or enterocyte subtype, a colon cancer classified under the colon cancer molecular subtype (CCMS) system as C1, C2, C3, C4, C5, or C6 subtype, a colon cancer classified under the CRC intrinsic subtype (CRCIS) system as Type A, Type B, or Type C subtype, or a colon cancer classified under the colorectal cancer subtyping consortium (CRCSC) classification system as CMS1, CMS2, CMS3, or CMS4. 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 undergone a therapy (e.g., chemotherapy, radiation, surgery or immunomodulatory therapy) . In some embodiments, the individual does not respond to a previous therapy (e.g., chemotherapy, radiation, surgery or immunomodulatory therapy) .

In various embodiments, the method described herein is used to treat colon cancer at different stages. In some embodiments, the method is used to treat stage I colon cancer. In some embodiments, the method is used to treat stage II (for example, stage IIA, IIB, or IIC) colon cancer. In some embodiments, the method is used to treat stage III (for example, stage IIIA, IIIB, or IIIC) colon cancer. In some embodiments, the method is used to treat stage IV (for example, stage IVA, IVB, or IVC) colon cancer. In some embodiments, the method is used to treat stage 0 colon cancer (i.e., carcinoma in situ) .

In some embodiments, the colon cancer is characterized with a genomic instability. In some embodiments, the genomic instability comprises at least one modification of genomic DNA. In some embodiments, the modification is a chromosomal instability (CIN) . In some embodiments, the modification is a loss of heterozygosity (e.g., a massive loss of chromosomal DNA) . In some embodiments, the modification is a microsatellite instability (MSI) . In some embodiments, the modification of genomic DNA comprises a modification of DNA methylation or histone modification. In some embodiments, the colon cancer is characterized with at least 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, or 18%lower total DNA methylation than normal tissue. In some embodiments, the modification of genomic DNA comprises a CpG island methylator phenotype (CIMP) . In some embodiments, the colon cancer is characterized with a modified CpG island methylation. In some embodiments the modified CpG island methylation comprises hypermethylation of a CpG-rich promoter.

In various embodiments, the colon cancer can be classified under different system as different subtype. Some examples of classification systems are described in for example, 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 some embodiments, the colon cancer is classified under the colon cancer subtype (CCS) system as CCS1. In some embodiments, the colon cancer is classified under the colon cancer subtype (CCS) system as CCS2. In some embodiments, the colon cancer is classified under the colon cancer subtype (CCS) system as CCS3.

In some embodiments, the colon cancer is classified under colorectal cancer assigner (CRCA system) as stem-like subtype. In some embodiments, the colon cancer is classified under colorectal cancer assigner (CRCA system) as inflammatory subtype. In some embodiments, the colon cancer is classified under colorectal cancer assigner (CRCA system) as transit-amplifying subtype. In some embodiments, the colon cancer is classified under colorectal cancer assigner (CRCA system) as enterocyte subtype.

In some embodiments, the colon cancer is classified under the colon cancer molecular subtype (CCMS) system as C1 subtype. In some embodiments, the colon cancer is classified under the colon cancer molecular subtype (CCMS) system as C2 subtype. In some embodiments, the colon cancer is classified under the colon cancer molecular subtype (CCMS) system as C3 subtype. In some embodiments, the colon cancer is classified under the colon cancer molecular subtype (CCMS) system as C4 subtype. In some embodiments, the colon cancer is classified under the colon cancer molecular subtype (CCMS) system as C5 subtype. In some embodiments, the colon cancer is classified under the colon cancer molecular subtype (CCMS) system as C6 subtype. In some embodiments, the colon cancer is classified under the colon cancer molecular subtype (CCMS) system as both C1 and C5 subtype.

In some embodiments, the colon cancer is classified under the CRC intrinsic subtype (CRCIS) system as Type A subtype (i.e., MMR-deficient epithelial subtype) . In some embodiments, the colon cancer is classified under the CRC intrinsic subtype (CRCIS) system as Type B subtype (i.e., epithelial proliferative subtype) . In some embodiments, the colon cancer is classified under the CRC intrinsic subtype (CRCIS) system as Type C subtype. In some embodiments, the colon cancer is classified under the colorectal cancer subtyping consortium (CRCSC) classification system as CMS1. In some embodiments, the colon cancer is classified under the colorectal cancer subtyping consortium (CRCSC) classification system as CMS2. In some embodiments, the colon cancer is classified under the colorectal cancer subtyping consortium (CRCSC) classification system as CMS3. In some embodiments, the colon cancer is classified under the colorectal cancer subtyping consortium (CRCSC) classification system as CMS4.

Methods of treatment

In some embodiments, methods disclosed herein comprise administering an effective amount of a DNA damaging agent. DNA damaging agents encompassed by the present disclosure include pharmaceutically acceptable compositions that cause DNA damages, including ssDNA damages and DSBs. In some embodiments, the DNA damaging agent directly attenuates or disrupts DNA synthesis and/or replication. In some embodiments, the DNA damaging agent reduces, blocks, or abolishes the expression and/or activity of one or more components of one or more DNA DSB repair pathways (including but not limited to HR pathway and NHEJ pathways) and/or ssDNA damage repair pathways. The DNA damaging agent may be a platinum-based compound, DNA cross-linker, a topoisomerase inhibitor, an ATRi, or a PARPi. In certain embodiments, the platinum-based compound may be cisplatin or carboplatin. In some embodiments, the topoisomerase inhibitor may be irinotecan or topotecan.

In some embodiments, methods disclosed herein comprise administering an effective amount of a PARP inhibitor. PARP inhibitors encompassed by the present disclosure include pharmaceutically acceptable compositions that inhibit the activity of the enzyme, poly (ADP-ribose) polymerase (PARP) .

In some embodiments, the PARP inhibitor is selected from the group consisting of: 3-aminobenzamine, BGD-290, CEP 9722, E7016, iniparib, niraparib, olaparib, rucaparib, talazoparib, and veliparib. In some embodiments, the PARP inhibitor is 3-aminobenzamine, BGD-290, CEP 9722, E7016, iniparib, niraparib, olaparib, rucaparib, 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 talazoparib. In some embodiments, the PARP inhibitor is rucaparib. In some embodiments, the PARP inhibitor is niraparib. In some embodiments, the PARP inhibitor is selected from the group consisting of a tetracycline compound, 4-hydroxyquinazoline and a derivative thereof, and a carboxamino-benzimidazole and a derivative thereof.

In some embodiments, methods disclosed herein comprise administering an effective amount of an ATRi. ATR inhibitors encompassed by the present disclosure include pharmaceutically acceptable compositions that inhibit the activity of ATR.

In some embodiments, the ATRi is selected from the group consisting of: Schisandrin B, NU6027, Dactolisib (NVP-BEZ235) , EPT-46464, Torin 2, VE-821, AZ20, Novartis's Tetrahydropyrazolo 1, 5-apyrazines lead, Novartis's Azabenzimidazole series lead, M4344 (VX-803) , BAY1895344, Berzosertib M6620 (VX-970) , and Ceralasertib AZD6738. In some embodiments, the ATRi is selected from the group consisting of AZD6738, M6620 (VX-970) , BAY1895344, and M4344 (VX-803) , which have progressed to phase I and II clinical trials in the last 8 years.

In some embodiments, the effective amount of the DNA damaging agent (e.g., PARP inhibitor or ATRi) is about 1 mg to about 1000 mg, such as about 10 mg to about 800 mg, about 100 mg to about 600 mg, or 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 any of 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 1000 mg.

In some embodiments, the effective amount of the DNA damaging agent (e.g., a PARP inhibitor or an ATRi) is no greater than about 1000 mg, such as no greater than about any of 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.

In some embodiments, the DNA damaging agent (e.g., PARP inhibitor or ATRi) is administered to the individual parenterally, including intravenous, intra-arterial, intraperitoneal, intrapulmonary, oral, inhalation, intravesicular, intramuscular, intra-tracheal, subcutaneous, intraocular, intrathecal, or transdermal. In some embodiments, the PARP inhibitor or ATRi is administered to the individual orally.

In some embodiments, a PARPi is administered in combination with an ATRi.

In some embodiments, the DNA damaging agent (e.g., PARP inhibitor or ATRi) is administered in combination with a second anti-cancer therapy or agent. In some embodiments, the anti-cancer therapy is a small molecule inhibitor, an antibody, a cellular therapy (i.e., a cell-based therapy) , or a nucleic acid. In some embodiments, the cellular therapy is an adoptive therapy, a T cell-based therapy, a natural killer (NK) cell-based therapy, a chimeric antigen receptor (CAR) -T cell therapy, a recombinant T cell receptor (TCR) T cell therapy, or a dendritic cell (DC) -based therapy. In some embodiments, the nucleic acid comprises a double-stranded RNA (dsRNA) , a small interfering RNA (siRNA) , or a small hairpin RNA (shRNA) . In some embodiments, the anti-cancer therapy is a chemotherapeutic agent, an anti-hormonal agent, an antimetabolite chemotherapeutic agent, a kinase inhibitor, a peptide, a gene therapy, a vaccine, a platinum-based chemotherapeutic agent, an immunotherapy, an antibody, or a checkpoint inhibitor. In some embodiments, the anti-cancer therapy is an FGFR-targeted therapy. In some embodiments, the anti-cancer therapy is a PTEN-targeted therapy. In some embodiments, the anti-cancer therapy is an RB1-targeted therapy. In some embodiments, the anti-cancer therapy is an EGFR-targeted therapy. In some embodiments, the anti-cancer therapy is a SMARCA4-targeted therapy. In some embodiments, the anti-cancer therapy is a TP53-targeted therapy. In some embodiments, the anti-cancer therapy is a KRAS-targeted therapy. In some embodiments, the anti-cancer therapy is a KRAS (G12C) -targeted therapy. In some embodiments, the anti-cancer therapy is an NF2-targeted therapy. In some embodiments, the anti-cancer therapy is a VHL-targeted therapy. In some embodiments, the anti-cancer therapy is a PBRM1-targeted therapy. In some embodiments, the anti-cancer therapy is an immunotherapy.

Reporting

In some embodiments, the methods provided herein comprise generating a report, and/or providing a report to party.

In some embodiments, a report according to the present disclosure comprises information about the presence or absence of a drug sensitive aberration, such as a drug sensitive mutation in any of the drug sensitive genes described herein. In some embodiments, a report according to the present disclosure comprises information about the presence or absence of a drug resistant aberration, such as a drug resistant mutation in any of the drug resistant genes described herein.

In one embodiment, a report according to the present disclosure indicates that a drug sensitive aberration, such as a drug sensitive mutation in any of the drug sensitive genes described herein (and/or a drug resistant aberration, such as a drug resistant mutation in any of the drug resistant genes described herein) is present in a sample obtained from the individual. In one embodiment, a report according to the present disclosure indicates that a drug sensitive aberration, such as a drug sensitive mutation in any of the drug sensitive genes described herein (and/or a drug resistant aberration, such as a drug resistant mutation in any of the drug resistant genes described herein) is not present in a sample obtained from the individual. In one embodiment, a report according to the present disclosure indicates that a drug sensitive aberration such as a drug sensitive mutation in any of the drug sensitive genes described herein (and/or a drug resistant aberration, such as a drug resistant mutation in any of the drug resistant genes described herein) has been detected in a sample obtained from the individual. In one embodiment, a report according to the present disclosure indicates that a drug sensitive aberration, such as a drug sensitive mutation in any of the drug sensitive genes described herein (and/or a drug resistant aberration, such as a drug resistant mutation in any of the drug resistant genes described herein) has not been detected in a sample obtained from the individual. In some embodiments, the report comprises an identifier for the individual from which the sample was obtained.

In some embodiments, the report includes information on the role of a drug sensitive aberration (e.g., a drug sensitive mutation in any of the drug sensitive genes described herein (and/or a drug resistant aberration, such as a drug resistant mutation in any of the drug resistant genes described herein) in colorectal cancer. Such information can include one or more of: information on prognosis of a colorectal cancer, information on resistance of a cancer to a DNA damaging agent (e.g., PARP inhibitor or ATRi) treatment; information on potential or suggested therapeutic options (e.g., such as treatment with a DNA damaging agent such as PARP inhibitor or ATRi, or combination therapy) ; or information on therapeutic options that should be avoided. In some embodiments, the report includes information on the likely effectiveness, acceptability, and/or advisability of applying a therapeutic option (e.g., a treatment comprising a DNA damaging agent such as PARP inhibitor or ATRi) to an individual having a colorectal cancer. In some embodiments, the report includes information or a recommendation on the administration of a treatment (e.g., a treatment comprising a DNA damaging agent such as PARP inhibitor or ATRi) .

In some embodiments, the information or recommendation includes the dosage of the treatment and/or a treatment regimen (e.g., in combination with other treatments) . In some embodiments, the report comprises information or a recommendation 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 treatments. In some embodiments, the report comprises information or a recommendation of 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 treatments.

Also provided herein are methods of generating a report according to the present disclosure. In some embodiments, a report according to the present disclosure is generated by a method comprising one or more of the following steps: obtaining a sample, such as a sample described herein, from an individual having colorectal cancer; detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes, or acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes; and generating a report. In some embodiments, the report generated is a personalized cancer report.

A report according to the present disclosure may be in an electronic, web-based, or paper form. The report may be provided to an individual or a patient, or to an individual or entity other than the individual or patient (e.g., other than the individual or patient with the cancer) , such as one or more of a caregiver, a physician, an oncologist, a hospital, a clinic, a third party payer, an insurance company, or a government entity. In some embodiments, the report is provided or delivered to the individual or entity within any of 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, about 45 days or more, or about 60 days or more from obtaining a sample from the individual (e.g., an individual having a cancer) . In some embodiments, the report is provided or delivered to an individual or entity within any of 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, about 45 days or more, or about 60 days or more from detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample obtained from the individual (e.g., an individual having a colorectal cancer) . In some embodiments, the report is provided or delivered to an individual or entity within any of 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, about 45 days or more, or about 60 days or more from acquiring knowledge of one or more drug sensitive aberrations (e.g., drug sensitive mutations) in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations (e.g., drug resistant mutations) in one or a plurality of drug resistant genes in a sample obtained from the individual (e.g., an individual having a colorectal cancer) .

Detection of Aberrations such as Mutations

In some embodiments, the drug sensitive mutation or drug resistant mutation is selected from the group consisting of splice site mutation, nonsense mutation, frameshift mutation, and missense mutation. In some embodiments, the drug sensitive mutation or drug resistant mutation is a deleterious or pathogenic (i.e., inactivating) mutation. Pathogenic inactivating mutations (loss-of-function) of certain genes can be determined by review of experimental evidence within the published scientific literature and review of critical regions that may be disrupted, including but not limited to frameshift, missense mutations, truncating mutations, deletions, copy number variations, nonsense mutations, and loss or deletion of the gene. Pathogenic or inactivating mutation includes but not limited to homozygous deletions, bi-allelic (double hit) mutations, splice site mutations (e.g., a 2nd or an additional splice site mutation) , frameshift mutations, and nonsense mutations in coding region, missense mutations with confirmed impact.

Drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) can be detected using any suitable method known in the art, such as a nucleic acid hybridization assay, immunofluorescence staining, western blot, an amplification-based assay (e.g., PCR) , a PCR-RFLP assay, real-time PCR, sequencing (e.g., Sanger sequencing or next-generation sequencing) , a screening analysis (e.g., using karyotype methods) , such as DNA sequencing, RNA-seq, ChIP-seq, DNase-seq, micrococcal nuclease (MNase) -seq (e.g., for detecting nucleosomal arrangement at gene regulatory region) , fluorescence in situ hybridization (FISH) , 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-spectrometric genotyping. Methods of analyzing samples, e.g., to detect a nucleic acid molecule, are described in U.S. Patent No. 9,340,830 and in WO2012092426A1, which are hereby incorporated by reference in their entirety.

In Situ Hybridization Methods

In some embodiments, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure are detected using an in situ hybridization method, such as a fluorescence in situ hybridization (FISH) method.

In some embodiments, FISH analysis is used to identify the chromosomal rearrangement resulting in the mutations as described herein. In some embodiments, FISH analysis is used to identify an RNA molecule or protein comprising one or more drug sensitive mutations or/or drug resistant mutations described herein. In some embodiments, FISH analysis is used to identify aberrant expression of an RNA or protein. In some embodiments, FISH analysis is used to identify aberrant modification of a DNA, an RNA, or a protein. Methods for performing FISH are known in the art and can be used in nearly any type of tissue. In some embodiments, protein probes are labeled (e.g., fluorescently or radiolabeled) and incubated with tissues that contain target proteins or receptors, and the interaction sites can be localized (e.g., via microscope) through detection of the labeled protein probe. In FISH analysis, nucleic acid probes which are detectably labeled, e.g. fluorescently labeled, are allowed to bind to specific regions of DNA, e.g., a chromosome, or an RNA, e.g., an mRNA, and then examined, e.g., through a microscope. DNA or RNA molecules are first fixed onto a slide, the labeled probe is then hybridized to the DNA or RNA molecules, and then visualization is achieved, e.g., using enzyme-linked label-based detection methods known in the art. Generally, the resolution of FISH analysis is on the order of detection of 60 to 100000 nucleotides, e.g., 60 base pairs (bp) up to 100 kilobase pairs of DNA. Nucleic acid probes used in FISH analysis comprise single stranded nucleic acids. Such probes are typically at least about 50 nucleotides in length. In some embodiments, probes comprise about 100 to about 500 nucleotides. Probes that hybridize with centromeric DNA and locus-specific DNA or RNA are available commercially, for example, from Vysis, Inc. (Downers Grove, Ill. ) , Molecular Probes, Inc. (Eugene, Oreg. ) or from Cytocell (Oxfordshire, UK) . Alternatively, probes can be made non-commercially from chromosomal or genomic DNA or other sources of nucleic acids (or polypeptides) through standard techniques. Examples of probes, labeling and hybridization methods are known in the art.

Several variations of FISH methods are known in the art and are suitable for use according to the methods of the disclosure, including single-molecule RNA FISH, Fiber FISH, Q-FISH, Flow-FISH, MA-FISH, break-away FISH, hybrid fusion-FISH, and multi-fluor FISH or mFISH. In some embodiments, proteins can be detected via immunofluorescence staining, e.g., using antibodies or antigen-binding fragments thereof.

Array-Based Methods

In some embodiments, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure are detected using an array-based method, such as array-based comparative genomic hybridization (CGH) methods. In array-based CGH methods, a first sample of nucleic acids (e.g., from a sample, such as from a tumor) is labeled with a first label, while a second sample of nucleic acids (e.g., a control, such as from a healthy cell/tissue) is labeled with a second label. In some embodiments, equal quantities of the two samples are mixed and co-hybridized to a DNA microarray of several thousand evenly spaced cloned DNA fragments or oligonucleotides, which have been spotted in triplicate on the array. After hybridization, digital imaging systems are used to capture and quantify the relative fluorescence intensities of each of the hybridized fluorophores. The resulting ratio of the fluorescence intensities is proportional to the ratio of the copy numbers of DNA sequences in the two samples. In some embodiments, where there are chromosomal deletions or multiplications, differences in the ratio of the signals from the two labels are detected and the ratio provides a measure of the copy number. Array-based CGH can also be performed with single-color labeling. In single color CGH, a control (e.g., control nucleic acid sample, such as from a healthy cell/tissue) is labeled and hybridized to one array and absolute signals are read, and a test sample (e.g., a nucleic acid sample obtained from an individual or from a tumor) is labeled and hybridized to a second array (with identical content) and absolute signals are read. Copy number differences are calculated based on absolute signals from the two arrays. In some embodiments, the array is use for detecting RNAs in the sample. In some embodiments, the resulting ratio of the fluorescence intensities is proportional to the ratio of the amount of RNA in the two samples, e.g., to reflect aberrant expression level. In some embodiments, the array is a protein array or protein chip.

Amplification-Based Methods

In some embodiments, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure are detected using an amplification-based method. As is known in the art, in such amplification-based methods, a sample of nucleic acids, such as a sample obtained from an individual or from a tumor, is used as a template in an amplification reaction (e.g., PCR) using one or more oligonucleotides or primers, e.g., such as one or more oligonucleotides or primers provided herein. The presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure in the sample can be determined based on the presence or absence of an amplification product. Quantitative amplification methods are also known in the art and may be used according to the methods provided herein. The known nucleotide sequence for genes is sufficient to enable one of skill in the art to routinely select primers to amplify any portion of the gene. Fluorogenic quantitative PCR can also be used. In fluorogenic quantitative PCR, quantitation is based on the amount of fluorescence signals, e.g., TaqMan and Sybr green.

Other amplification methods suitable for use according to the methods provided herein include, e.g., ligase chain reaction (LCR) , transcription amplification, self-sustained sequence replication, dot PCR, and linker adapter PCR.

Sequencing

In some embodiments, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure are detected using a sequencing method. Any method of sequencing known in the art can be used to detect one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure. Exemplary sequencing methods that may 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 procedures may also be used, e.g., including sequencing by mass spectrometry. In some embodiments, the entire gene or gene product (e.g., RNA, polypeptide) is sequenced. In some embodiments, a relevant portion of a gene or gene product (e.g., RNA, polypeptide) is sequenced, such as a nucleic acid or polypeptide fragment known to contain a mutation or modification. In some embodiments, the aberration comprises aberrant expression. In some embodiments, the aberration comprises aberrant modification (e.g., on DNA, RNA, or polypeptide level) .

In some embodiments, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure are detected using hybrid capture-based sequencing (hybrid capture-based next-generation sequencing (NGS) ) , e.g., using adaptor ligation-based libraries. See, e.g., Frampton, G. M. et al. (2013) Nat. Biotech. 31: 1023-1031. In some embodiments, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure are detected using next-generation sequencing (NGS) . Next-generation sequencing includes any sequencing method that determines the nucleotide sequence of either individual nucleic acid molecules or clonally expanded proxies for individual nucleic acid molecules in a highly parallel fashion (e.g., greater than 10 ⁵ molecules may be sequenced simultaneously) . Next generation sequencing methods suitable for use according to the methods provided herein are known in the art and include, without limitation, massively parallel short-read sequencing, template-based sequencing, pyrosequencing, real-time sequencing comprising imaging the continuous incorporation of dye-labeling nucleotides during DNA synthesis, nanopore sequencing, sequencing by hybridization, nano-transistor array based sequencing, polony sequencing, scanning tunneling microscopy (STM) -based sequencing, or nanowire-molecule sensor based sequencing. See, e.g., Metzker, M. (2010) Nature Biotechnology Reviews 11:31-46, which is hereby incorporated by reference. Exemplary NGS methods and platforms that may be used to detect one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure include, without limitation, the HeliScope Gene Sequencing system from Helicos BioSciences (Cambridge, MA., USA) , the PacBio RS system from Pacific Biosciences (Menlo Park, CA, USA) , massively parallel short-read sequencing such as the Solexa sequencer and other methods and platforms from Illumina Inc. (San Diego, CA, USA) , 454 sequencing from 454 LifeSciences (Branford, CT, USA) , Ion Torrent sequencing from ThermoFisher (Waltham, MA, USA) , or the SOLiD sequencer from Applied Biosystems (Foster City, CA, USA) . Additional exemplary methods and platforms that may be used to detect one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure include, without limitation, the Genome Sequencer (GS) FLX System from Roche (Basel, CHE) , the G. 007 polonator system, the Solexa Genome Analyzer, HiSeq 2500, HiSeq3000, HiSeq 4000, and NovaSeq 6000 platforms from Illumina Inc. (San Diego, CA, USA) .

In some embodiments of any of the methods provided herein, the methods comprise providing a sample from an individual having a colorectal cancer, wherein the sample comprises one or more polypeptides. In some embodiments, the methods further comprise preparing a protein or polypeptide library (e.g., for mass-spec) from the one or more polypeptides in the sample. Sample or library preparation methods for protein sequencing or mass spectrometry are well known. E. g., see Laura Restrepo-Pérez et al (2018) Nat Nanotechnol, 13: 786–796) .

In some embodiments of any of the methods provided herein, the methods comprise providing a sample from an individual having a colorectal cancer, wherein the sample comprises one or more nucleic acids. In some embodiments, the methods further comprise preparing a nucleic acid sequencing library from the one or more nucleic acids in the sample. Methods for the preparation of nucleic acid sequencing libraries, e.g., suitable for any of the sequencing methods described herein (e.g., 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 (e.g., including the steps of adding sample indexes and/or barcodes) are known in the art. In some embodiments, the sequencing library is amplified using a PCR. In some embodiments, the sequencing library is amplified as described in Frampton et al

Nat Biotechnol, 31: 1023-1031. In some embodiments, the methods further comprise selectively enriching for one or more nucleic acids (e.g., one or more nucleic acids comprising one or more gene alterations described herein) to produce an enriched sample. In some embodiments, the selectively enriching comprises combining a bait, such as a bait described herein, with a sample (e.g., the library) , thereby hybridizing the bait to the one or more nucleic acids in the sample (e.g., in the library) , and producing nucleic acid hybrids; and isolating the nucleic acid hybrids to produce an enriched sample. In some embodiments, the selectively enriching is performed as described in Frampton et al (2013) Nat Biotechnol, 31: 1023-1031. In some embodiments, the methods further comprise amplifying, e.g. using PCR, the nucleic acids in the enriched sample. In some embodiments, the methods further comprise sequencing the enriched sample, thereby producing a plurality of sequencing reads. In some embodiments, the sequencing is performed using any method for sequencing known in the art or provided herein. In some embodiments, the sequencing is performed using an Illumina sequencer. In some embodiments, the sequencing is performed as described in Frampton et al (2013) Nat Biotechnol, 31: 1023-1031. In some embodiments, the methods further comprise analyzing the plurality of sequencing reads, e.g., for the presence of one or more gene alterations described herein. In some embodiments, the analyzing step comprises aligning the plurality of sequencing reads to the human genome, e.g., to human genome version hg19, e.g., using any suitable methods, such as a BWA aligner. In some embodiments, the analyzing step further comprises removing PCR duplicate reads, and/or collecting sequence metrics (e.g., using Picard 1.47 and/or Samtools) . In some embodiments, the analyzing step comprises performing local alignment optimization, e.g., using GATK. In some embodiments, the analyzing step further comprises variant calling. In some embodiments, the analyzing step comprises detecting base substitutions, e.g., using a Bayesian methodology. In some embodiments, the analyzing step comprises detecting indels, e.g., using the Bruijn approach. In some embodiments, the analyzing step comprises detecting copy number alterations, e.g., using comparative genomic hybridization-like methods. In some embodiments, the analyzing step comprises detecting genomic rearrangements and/or gene fusions, e.g., 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 methods further comprise detecting, based on the analyzing step, one or more gene alterations described herein.

Baits, capturing polypeptide, capturing nucleic acid, probes, primers, and oligonucleotide

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to a plurality of drug sensitive genes and/or a plurality of drug resistant genes, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to expression products (e.g., polypeptide) (or portion thereof) of a plurality of drug sensitive genes and/or a plurality of drug resistant genes. 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 to hybridize to a plurality of drug sensitive genes and/or a plurality of drug resistant genes, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to expression products (e.g., polypeptide) of a plurality of drug sensitive genes and/or a plurality of drug resistant genes.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 or 2, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 or 2. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 or 2, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 or 2.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 3a) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3a) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3a) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3a) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 3b) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 3b) . 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 to hybridize to at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 3b) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 3b) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3c) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3c) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3c) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3c) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3d) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3d) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3d) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 3d) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or all drug sensitive genes provided in Table 3e) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or all drug sensitive genes provided in Table 3e) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or all drug sensitive genes provided in Table 3e) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, or all drug sensitive genes provided in Table 3e) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 4, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 4. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 4, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 4.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4a) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4a) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4a) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4a) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4b) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4b) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4b) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4b) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4c) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4c) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4c) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4c) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4d) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4d) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4d) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table 4d) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4e) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4e) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4e) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4e) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4f) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4f) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4f) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 60, 70, or all drug sensitive genes provided in Table 4f) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 5 or 6, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 5 or 6. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 5 or 6, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 5 or 6.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7a) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7a) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7a) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7a) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7b) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7b) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7b) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7b) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 7c) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 7c) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 7c) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 7c) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7d) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7d) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7d) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 7d) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 7e) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 7e) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 7e) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 7e) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8, or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8, or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8a) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8a) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8a) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8a) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8b) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8b) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8b) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, or all drug resistant genes provided in Table 8b) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8c) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8c) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8c) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8c) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8d) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8d) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8d) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table 8d) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 8e) , or RNAs encoded thereof. In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 8e) . 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 8e) , or RNAs encoded thereof. In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, or all drug resistant genes provided in Table 8e) .

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, or all drug sensitive genes provided in Table 1 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 5 (or RNAs encoded thereof) . In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 1 and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 5. 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 to hybridize to at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 1 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 5 (or RNAs encoded thereof) . In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 1 and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 5.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6 (or RNAs encoded thereof) . In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6 (or RNAs encoded thereof) . In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 1 and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 2 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6 (or RNAs encoded thereof) . In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 2 and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6. 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 to hybridize to at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 2 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6 (or RNAs encoded thereof) . In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, or all drug sensitive genes provided in Table 2 and at least any of 1, 5, 10, 20, 30, or all drug resistant genes provided in Table 6.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7 (or RNAs encoded thereof) . In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3 and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7 (or RNAs encoded thereof) . In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug sensitive genes provided in Table 3 and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, or all drug resistant genes provided in Table 7.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B (or RNAs encoded thereof) . In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A and at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B (or RNAs encoded thereof) . In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, or all drug sensitive genes provided in Table A and at least any of 1, 5, 10, 20, 30, 40, or all drug resistant genes provided in Table B.

In some embodiments, there is provided a plurality of capture nucleic acid molecules (or probes, primers, oligonucleotides, or baits each comprising a capture nucleic acid molecule) configured to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug sensitive genes provided in Table 4 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8 (or RNAs encoded thereof) . In some embodiments, there is provided a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug sensitive genes provided in Table 4 and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8. 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 to hybridize to at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug sensitive genes provided in Table 4 (or RNAs encoded thereof) and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8 (or RNAs encoded thereof) . In some embodiments, there is provided a kit comprising a plurality of capture polypeptide molecules (e.g., polypeptide, antibody or fragment thereof, or baits each comprising a capture polypeptide molecule) configured to bind to the polypeptide (or portion thereof) encoded by at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug sensitive genes provided in Table 4 and at least any of 1, 5, 10, 20, 30, 40, 50, 100, 200, 300, or all drug resistant genes provided in Table 8.

Baits

Provided herein are baits suitable for the detection of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure or for enrichment of one or more drug sensitive genes and/or drug resistant genes.

In some embodiments, the bait comprises a capture polypeptide molecule configured to bind to a target polypeptide or a fragment or portion thereof. In some embodiments, the fragment comprises (or is) at least about 5 aa in length. In some embodiments, the capture polypeptide molecule is a polypeptide (e.g., a ligand of a receptor encoded by a drug sensitive gene/drug resistant 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 aa in length, such as at least about any of 15 aa, 20 aa, 30 aa, 40 aa, 50 aa, 100 aa, 1000 aa, or longer.

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) between about 5 and about 25 nucleotides, between about 5 and about 300 nucleotides, between about 100 and about 300 nucleotides, between about 130 and about 230 nucleotides, or between about 150 and about 200 nucleotides.

In some embodiments, the capture nucleic acid molecule is between about 5 and about 25 nucleotides, between about 5 and about 300 nucleotides, between about 100 and about 300 nucleotides, between about 130 and about 230 nucleotides, or between about 150 and 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, about 225 nucleotides, about 250 nucleotides, about 275 nucleotides, or about 300 nucleotides in length. In some embodiments, the capture nucleic acid molecule comprises (or 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 length. 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 length. In some embodiments, the capture nucleic acid molecule is between about 5 and about 25 nucleotides in length, between about 5 and about 300 nucleotides in length, between about 100 and about 300 nucleotides in length, between about 130 and about 230 nucleotides in length, or between about 150 and about 200 nucleotides in length.

In some embodiments, the capture nucleic acid molecule is a DNA, RNA, or a DNA/RNA molecule.

In some embodiments, a bait provided herein comprises a DNA, RNA, or a DNA/RNA molecule. In some embodiments, a bait provided herein comprises a polypeptide, or antibody or antigen-binding fragment thereof. In some embodiments, a bait provided herein includes a label or a tag. In some embodiments, the label or tag is a radiolabel, a fluorescent label, an enzymatic label, a sequence tag, biotin, or another ligand. In some embodiments, a bait provided herein includes a detection reagent such as a fluorescent marker. In some embodiments, a bait provided herein includes (e.g., is conjugated to) an affinity tag, e.g., that allows capture and isolation of a hybrid formed by a bait and a nucleic acid hybridized to the bait. In some embodiments, the affinity tag is an antibody, an antibody fragment, biotin, or any other suitable affinity tag or reagent known in the art. In some embodiments, a bait is suitable for solution phase hybridization.

Baits can be produced and used according to methods known in the art, e.g., as described in WO2012092426A1 and/or or in Frampton et al (2013) Nat Biotechnol, 31: 1023-1031, incorporated herein by reference. For example, biotinylated baits (e.g., RNA baits) can be produced by obtaining a pool of synthetic long oligonucleotides, originally synthesized on a microarray, and amplifying the oligonucleotides to produce the bait sequences. In some embodiments, the baits are produced by adding an RNA polymerase promoter sequence at one end of the bait sequences, and synthesizing RNA sequences using RNA polymerase. In one embodiment, libraries of synthetic oligodeoxynucleotides can be obtained from commercial suppliers, such as Agilent Technologies, Inc., and amplified using known nucleic acid amplification methods. Any suitable protein (e.g., antibody) synthesis methods can be used herein to make baits.

In some embodiments, a bait provided herein is at least about 10 aa in length. In some embodiments, a bait provided herein comprises a target-specific bait sequence (e.g., a capture polypeptide molecule described herein) and universal tails on each end. In some embodiments, the target-specific sequence, e.g., a capture polypeptide molecule described herein, is at least about 10 aa in length, such as at least about any of 15 aa, 20 aa, 30 aa, 40 aa, 50 aa, 100 aa, 1000 aa, or longer.

In some embodiments, a bait provided herein is between about 100 nucleotides and about 300 nucleotides. In some embodiments, a bait provided herein is between about 130 nucleotides and about 230 nucleotides. In some embodiments, a bait provided herein is between about 150 nucleotides and about 200 nucleotides. In some embodiments, a bait provided herein comprises a target-specific bait sequence (e.g., a capture nucleic acid molecule described herein) and universal tails on each end. In some embodiments, the target-specific sequence, e.g., a capture nucleic acid molecule described herein, is between about 10 nucleotides and about 300 nucleotides. In some embodiments, the target-specific sequence, e.g., a capture nucleic acid molecule described herein, is between about 100 nucleotides and about 200 nucleotides. In some embodiments, the target-specific sequence, e.g., a capture nucleic acid molecule described herein, is between about 120 nucleotides and about 170 nucleotides. In some embodiments, the target-specific sequence, e.g., a capture nucleic acid molecule described herein, is about 150 nucleotides or about 170 nucleotides. In some embodiments, a bait provided herein comprises an oligonucleotide comprising about 200 nucleotides, of which about 150 nucleotides or about 170 nucleotides are target-specific (e.g., a capture nucleic acid molecule described herein) , and the other 50 nucleotides or 30 nucleotides (e.g., 25 or 15 nucleotides on each end of the bait) are universal arbitrary tails, e.g., suitable for PCR amplification.

Probes

Also provided herein are probes, e.g., nucleic acid molecules, suitable for the detection of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure. In some embodiments, a probe provided herein comprises a nucleic acid sequence configured to hybridize to a target nucleic acid molecule comprising one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure or a fragment or portion thereof.

In some embodiments, the probe comprises a nucleic acid molecule which is a DNA, RNA, or a DNA/RNA molecule. In some embodiments, the probe comprises a nucleic acid molecule comprising any of between about 10 and about 20 nucleotides, between about 12 and about 20 nucleotides, between about 10 and about 1000 nucleotides, between about 50 and about 500 nucleotides, between about 100 and about 500 nucleotides, between about 100 and about 300 nucleotides, between about 130 and about 230 nucleotides, or between about 150 and about 200 nucleotides. In some embodiments, the probe comprises a nucleic acid molecule comprising any of 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, 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 any of between about 40 nucleotides and about 50 nucleotides, about 50 nucleotides and about 100 nucleotides, about 100 nucleotides and about 150 nucleotides, about 150 nucleotides and about 200 nucleotides, about 200 nucleotides and about 250 nucleotides, about 250 nucleotides and about 300 nucleotides, about 300 nucleotides and about 350 nucleotides, about 350 nucleotides and about 400 nucleotides, about 400 nucleotides and about 450 nucleotides, about 450 nucleotides and about 500 nucleotides, about 500 nucleotides and about 550 nucleotides, about 550 nucleotides and about 600 nucleotides, about 600 nucleotides and about 650 nucleotides, about 650 nucleotides and about 700 nucleotides, about 700 nucleotides and about 750 nucleotides, about 750 nucleotides and about 800 nucleotides, about 800 nucleotides and about 850 nucleotides, about 850 nucleotides and about 900 nucleotides, about 900 nucleotides and about 950 nucleotides, or about 950 nucleotides and about 1000 nucleotides. In some embodiments, the probe comprises a nucleic acid molecule comprising between about 12 and about 20 nucleotides.

In some embodiments, a probe provided herein includes a label or a tag. In some embodiments, the label or tag is a radiolabel (e.g., a radioisotope) , a fluorescent label (e.g., a fluorescent compound) , an enzymatic label, an enzyme co-factor, a sequence tag, biotin, or another ligand. In some embodiments, a probe provided herein includes a detection reagent such as a fluorescent marker. In some embodiments, a probe provided herein includes (e.g., is conjugated to) an affinity tag, e.g., that allows capture and isolation of a hybrid formed by a probe and a nucleic acid hybridized to the probe. In some embodiments, the affinity tag is an antibody, an antibody fragment, biotin, or any other suitable affinity tag or reagent known in the art. In some embodiments, a probe is suitable for solution phase hybridization.

In some embodiments, one or more probes provided herein are suitable for use in in situ hybridization methods, e.g., as described above, such as FISH.

Chromosomal probes, e.g., for use in the FISH methods described herein, are typically about 50 to about 10 ⁵ nucleotides in length. Longer probes typically comprise smaller fragments of about 100 to about 500 nucleotides. Probes that hybridize with centromeric DNA and locus-specific DNA are available commercially, for example, from Vysis, Inc. (Downers Grove, Ill. ) , Molecular Probes, Inc. (Eugene, Oreg. ) or from Cytocell (Oxfordshire, UK) . Alternatively, probes can be made non-commercially from chromosomal or genomic DNA through standard techniques. For example, sources of DNA that can be used include genomic DNA, cloned DNA sequences, somatic cell hybrids that contain one, or a part of one, chromosome (e.g., human chromosome) along with the normal chromosome complement of the host, and chromosomes purified by flow cytometry or microdissection. The region of interest can be isolated through cloning, or by site-specific amplification via PCR. Probes of the disclosure may also hybridize to RNA molecules, e.g., mRNA.

In some embodiments, probes, such as probes for use in the FISH methods described herein, are labeled such that a chromosomal region or a region on an RNA to which the probes hybridize can be detected. Probes typically are directly labeled with a fluorophore, allowing the probe to be visualized without a secondary detection molecule. Probes can also be labeled by nick translation, random primer labeling or PCR labeling. Labeling may be accomplished using fluorescent (direct) -or haptene (indirect) -labeled nucleotides. Representative, non-limiting examples of labels include: AMCA-6-dUTP, CascadeBlue-4-dUTP, Fluorescein-12-dUTP, Rhodamine-6-dUTP, TexasRed-6-dUTP, Cy3-6-dUTP, Cy5-dUTP, Biotin (BIO) -11-dUTP, Digoxygenin (DIG) -11-dUTP and Dinitrophenyl (DNP) -11-dUTP. Probes can also be indirectly labeled with biotin or digoxygenin, or labeled with radioactive isotopes such as ³²P and ³H, and secondary detection molecules are used, or further processing is performed, to visualize the probes. For example, a probe labeled with biotin can be detected by avidin conjugated to a detectable marker, e.g., avidin can be conjugated to an enzymatic marker such as alkaline phosphatase or horseradish peroxidase. Enzymatic markers can be detected in standard colorimetric reactions using a substrate and/or a catalyst for the enzyme. Catalysts for alkaline phosphatase include 5-bromo-4-chloro-3-indolylphosphate and nitro blue tetrazolium. Diaminobenzoate can be used as a catalyst for horseradish peroxidase. Probes can also be prepared such that a fluorescent or other label is added after hybridization of the probe to its target to detect that the probe hybridized to the target. For example, probes can be used that have antigenic molecules incorporated into the nucleotide sequence. After hybridization, these antigenic molecules are detected, for example, using specific antibodies reactive with the antigenic molecules. Such antibodies can, for example, themselves incorporate a fluorochrome, or can be detected using a second antibody with a bound fluorochrome. For fluorescent probes, e.g., used in FISH techniques, fluorescence can be viewed with a fluorescence microscope equipped with an appropriate filter for each fluorophore, or by using dual or triple band-pass filter sets to observe multiple fluorophores. Alternatively, techniques such as flow cytometry can be used to examine the hybridization pattern of the chromosomal probes.

Oligonucleotides

In some aspects, provided herein are oligonucleotides, e.g., useful as primers. In some embodiments, an oligonucleotide, e.g., a primer, provided herein comprises a nucleotide sequence configured to hybridize to a target nucleic acid molecule comprising one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure or a fragment or portion thereof. In some embodiments, the aberration comprises aberrant expression level. In some embodiments, the aberration comprises aberrant modification.

In some embodiments, an oligonucleotide, e.g., a primer, provided herein may be useful for initiating DNA synthesis via PCR or a sequencing method. In some embodiments, the oligonucleotide may be used to amplify a nucleic acid molecule comprising one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure, or a fragment thereof (e.g., known to contain a mutation) , e.g., using PCR. In some embodiments, the oligonucleotide may be used to sequence a nucleic acid molecule comprising one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure, or a fragment thereof.

In some embodiments, pairs of oligonucleotides, e.g., pairs of primers, are provided herein, which are configured to hybridize to a nucleic acid molecule comprising one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure, or a fragment thereof. In some embodiments, a pair of oligonucleotides of the disclosure may be used for directing amplification of a nucleic acid molecule or fragment thereof comprising one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure, e.g., using a PCR reaction.

In some embodiments, an oligonucleotide, e.g., a primer, provided herein is a single stranded nucleic acid molecule, e.g., for use in sequencing or amplification methods. In some embodiments, an oligonucleotide provided herein is a double stranded nucleic acid molecule. In some embodiments, a double stranded oligonucleotide is treated, e.g., denatured, to separate its two strands prior to use, e.g., in sequencing or amplification methods. Oligonucleotides provided herein comprise a nucleotide sequence of sufficient length to hybridize to their target and to prime the synthesis of extension products, e.g., during PCR or sequencing.

In some embodiments, an oligonucleotide, e.g., a primer, provided herein comprises 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, an oligonucleotide provided herein comprises between about 10 and about 30 deoxyribonucleotides or ribonucleotides. In some embodiments, an oligonucleotide provided herein comprises between about 10 and about 25 deoxyribonucleotides or ribonucleotides, including for example about 10 and about 20, about 10 and about 15, about 12 and about 20, or about 17 and about 20 deoxyribonucleotides or ribonucleotides. In some embodiments, the length and nucleotide sequence of an oligonucleotide provided herein is 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 (e.g., buffers, temperature) , and the nucleotide composition of the nucleotide sequence of the oligonucleotide or of its target complementary sequence.

Nucleic Acid or Polypeptide Samples

A variety of materials (such as tissues) can be the source of the nucleic acid (e.g., DNA or RNA) or polypeptide samples used in the methods provided herein. For example, the source of the sample can be solid tissue as from a fresh, frozen and/or preserved organ, tissue sample, biopsy, resection, smear, or aspirate; blood or any blood constituents; bodily fluids such as cerebrospinal fluid, amniotic fluid, urine, saliva, sputum, peritoneal fluid or interstitial fluid; or cells from any time in gestation or development of an individual. In some embodiments, the source of the sample is blood or blood constituents. In some embodiments, the source of the sample is a tumor sample, e.g., a colon cancer sample. In some embodiments, the sample is or comprises biological tissue or fluid. In some embodiments, the sample can contain compounds that are not naturally intermixed with the tissue in nature, such as preservatives, anticoagulants, buffers, fixatives, nutrients, antibiotics or the like. In some embodiments, the sample comprises genomic or subgenomic DNA fragments, or RNA, such as mRNA isolated from a sample, e.g., 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 polypeptide (s) , such as post-translational modified polypeptides. In some embodiments, the tissue is preserved as a frozen sample or as a formaldehyde-or paraformaldehyde-fixed paraffin-embedded (FFPE) tissue preparation. For example, the sample can be embedded in a matrix, e.g., an FFPE block or a frozen sample.

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 acids. In some embodiments, the sample comprises circulating tumor DNA (ctDNA) .

In some embodiments, a sample may be or comprise bone marrow; a bone marrow aspirate; blood; blood cells; ascites; tissue or fine needle biopsy samples; cell-containing body fluids; free floating nucleic acids; sputum; saliva; urine; cerebrospinal fluid, peritoneal fluid; pleural fluid; feces; lymph; gynecological fluids; skin swabs; vaginal swabs; oral swabs; nasal swabs; washings or lavages such as ductal lavages or bronchoalveolar lavages; aspirates; scrapings; bone marrow specimens; tissue biopsy specimens; surgical specimens; other body fluids, secretions, and/or excretions; and/or cells therefrom. In some embodiments, a biological sample is or comprises cells obtained from an individual.

In some embodiments, a sample is a primary sample obtained directly from a source of interest by any appropriate means. For example, in some embodiments, a primary biological sample is obtained by a method chosen from biopsy (e.g., fine needle aspiration or tissue biopsy) , surgery, or collection of body fluid (e.g., blood, lymph, or feces) . In some embodiments, as will be clear from context, the term “sample” refers to a preparation that is obtained by processing (e.g., by removing one or more components of and/or by adding one or more agents to) a primary sample. Such a processed sample may comprise, for example nucleic acids or proteins extracted from a sample or obtained by subjecting a primary sample to techniques such as amplification or reverse transcription of mRNA, or isolation and/or purification of certain components.

In some embodiments, the sample comprises tumor nucleic acids, such as nucleic acids from a tumor or a cancer sample, e.g., genomic DNA, RNA, or cDNA derived from RNA, from a tumor or cancer sample. In some embodiments, the sample comprises tumor polypeptides, such as polypeptides from a tumor or a cancer sample. In certain embodiments, a tumor nucleic acid or polypeptide sample is purified or isolated (e.g., it is removed from its natural state) .

In some embodiments, the sample is a control nucleic acid sample or a reference nucleic acid sample, e.g., genomic DNA, RNA, or cDNA derived from RNA, not containing an aberration (e.g., mutation, or aberrant expression/activity/modification) described herein. In some embodiments, the sample is a control polypeptide sample or a reference polypeptide sample, not containing an aberration (e.g., mutation, or aberrant expression/activity/modification) described herein. In certain embodiments, the reference or control nucleic acid or polypeptide sample comprises a wild type or a non-mutated sequence. In certain embodiments, the reference nucleic acid or polypeptide sample is purified or isolated (e.g., it is removed from its natural state) . In other embodiments, the reference nucleic acid or polypeptide sample is from a non- tumor sample, e.g., a blood control, a normal adjacent tumor (NAT) , or any other non-cancerous sample from the same or a different subject.

Systems, Software, and Devices

In some other aspects, provided herein are non-transitory computer-readable storage media. In some embodiments, the non-transitory computer-readable storage media comprise one or more programs for execution by one or more processors of a device, the one or more programs including instructions which, when executed by the one or more processors, cause the device to perform a method according to any of the embodiments described herein.

In some aspects, provided herein are systems comprising one or more processors and a non-transitory computer-readable storage media.

In some embodiments, a system of the disclosure 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 for performing a method.

In some embodiments, the method comprises one or more of: (a) sequencing one or more nucleic acids or polypeptides, thereby producing a plurality of sequencing reads, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyzing the plurality of sequencing reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure; and (c) detecting, based on the analyzing step, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure in the sample.

In some embodiments, a system of the disclosure comprises a memory configured to store one or more program instructions; and one or more processors configured to execute the one or more program instructions.

In some embodiments, 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 or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure; and (c) detect, based on the analyzing, one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure.

In some embodiments of the any of the systems provided herein, the one or more processors, and the non-transitory computer readable storage medium comprising one or more programs executable by the one or more processors are within a device. In some embodiments, the non-transitory computer-readable storage media comprise one or more programs for execution by one or more processors of the device, the one or more programs including instructions which, when executed by the one or more processors, cause the device to perform the method according to any of the embodiments described herein.

Kits

Also provided herein are kits for detecting one or more drug sensitive aberrations (e.g., drug sensitive mutations) and/or drug resistant aberrations (e.g., drug resistant mutations) of the disclosure. In some embodiments, the kit comprises a reagent (e.g., one or more oligonucleotides, primers, probes or baits of the present disclosure) for detecting a wild-type counterpart of the drug sensitive genes and/or drug resistant genes. In some embodiments, the reagent comprises one or more oligonucleotides, primers, probes or baits of the present disclosure capable of hybridizing to a nucleic acid molecule comprising one or more drug sensitive mutations and/or drug resistant mutations (or with aberrant expression/activity/modification) of the disclosure, or to a wild-type counterpart. In some embodiments, the reagent comprises one or more baits (e.g., polypeptide, antibody or fragment thereof) of the present disclosure capable of bind to one or more polypeptides (e.g., wild-type, or with mutation or aberrant expression/activity/modification) encoded by one or more drug sensitive genes and/or drug resistant genes described herein.

In some embodiments, the kit is for use according to any protein or polypeptide detection assay known in the art or described herein, such as mass spectrometry (e.g., tandem mass spectrometry) , a reporter assay (e.g., a fluorescence-based assay) , immunoblots such as a Western blot, immunoassays such as enzyme-linked immunosorbent assays (ELISA) , immunohistochemistry, other immunological assays (e.g., fluid or gel precipitin reactions, immunodiffusion, immunoelectrophoresis, radioimmunoassay (RIA) , immunofluorescent assays) , and analytic biochemical methods (e.g., electrophoresis, capillary electrophoresis, high performance liquid chromatography (HPLC) , thin layer chromatography (TLC) , or hyperdiffusion chromatography) . In some embodiments, the kit further comprises instructions for detecting a polypeptide encoded by a gene comprising one or more alterations of the disclosure, e.g., using one or more antibodies of the present disclosure.

EXAMPLES

The invention will be more fully understood by reference to the following examples. They should not, however, be construed as limiting the scope of the invention. It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims.

Example 1: Identification of drug sensitive genes and drug resistant genes in cancer cells

This example provides exemplary methods for identifying drug sensitive genes and/or drug resistant genes of DNA damaging agents such as PARPi and ATRi. Briefly, a cancer cell library carrying sgRNA ^iBAR targeting cancer-related genes was constructed for Cas9-mediated gene knock-out (KO) . By examining anti-cancer drug killing efficacy of the Cas9 ⁺ sgRNA ^iBAR cancer cell library constructed, genes conferring resistant phenotype or sensitive phenotype to PARPi or ATRi killing after KO can be identified. FIGs. 1-2 show the exemplary workflow.

1. Design and construction of sgRNA ^iBAR library

Based on public databases, genes with DNA mutation frequency ≥5%and RNA expression level up-or down-regulated by more than 2-fold from patients with stage III and IV colorectal cancer (expressed in cell, or on cell surface) were selected as library genes for further sgRNA ^iBAR design (total 1323 genes) .

sgRNA ^iBAR library was designed and constructed similarly as 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 of which are incorporated herein by reference in their entirety. Briefly, 1323 genes selected above were retrieved from UCSC human genome. sgRNAs targeting each gene were designed using the DeepRank algorithm (see Zhu et al.) , each gene had three different targeting sgRNAs, and four 6-bp iBARs (iBAR ₆s) were randomly assigned to each sgRNA ( “sgRNA ^iBAR” ) . The internal barcode sequence was designed to be placed in the tetra loop of the gRNA scaffold outside of the Cas9-sgRNA ribonucleoprotein complex, which did not affect the activity of its upstream guide sequence. In addition, 500 control sgRNAs not targeting any human genes were designed as negative control, and four iBAR ₆s were randomly assigned to each control sgRNA ( “control sgRNA ^iBAR” ) . The designed CRISPR sgRNA ^iBAR library therefore included a total of 17876 sgRNAs ^iBAR (target and control) .

DNA oligonucleotides encoding the sgRNAs ^iBAR were designed and synthesized (by Twist Bioscience) , then PCR amplified. PCR products were purified with PCR purification kit, then cloned via Golden Gate cloning into lentiviral sgRNA ^iBAR-expressing backbone modified in house based on pLenti-sgRNA-Lib (addgene #53121) to obtain sgRNA ^iBAR plasmids, which encodes 15876 sgRNAs ^iBAR covering 1323 human genes (3 sets of sgRNA ^iBAR for each gene targeting 3 different target sites, each set of sgRNA ^iBAR contains 4 sgRNAs ^iBAR) , and 2000 control sgRNAs ^iBAR targeting 500 non-gene regions (1 set of sgRNA ^iBAR for each non-gene region, each set of sgRNA ^iBAR contains 4 sgRNAs ^iBAR) .

In order to ensure the abundance of sgRNAs ^iBAR in the cancer cell library (at least 1000-fold coverage for each sgRNA ^iBAR) , 10 electroporation reactions were performed using sgRNA ^iBAR plasmids obtained above. For each electroporation reaction, 1 μL sgRNA ^iBAR plasmids were added into a sterile 1.5 mL Eppendorf tube, 50 μL competent cells (E. coli) were further added to the tube and swirled, then electroporation was conducted. 950 μL Super Optimal Broth (SOC) medium without antibiotics was immediately added to each reaction tube, gently pipetted to mix, then incubated in a shaker at 37℃ and 225 rpm for 1 hour. The resulting bacteria were transferred to 1 L LB liquid medium supplemented with Ampicillin, cultured overnight in a shaker at 37℃ and 225 rpm. The next day, plasmid extraction was performed on the obtained bacteria using

Plasmid Purification Kit (QIAGEN, #12391) .

sgRNA ^iBAR library lentiviruses were obtained using standard protocol. Briefly, 1×10 ⁷ 293T cells were placed in a 150 mm cell culture dish, 20 mL cell culture medium was added, then 293T cells were cultured overnight in a 37℃, 5%CO ₂ incubator. The next day, culture medium was discarded, 10 mL fresh serum-free medium was added to the 293T cell. The transfection complex was prepared using serum-free medium (4 mL) , sgRNA ^iBAR library plasmids obtained above (20 μg) , pCMVR8.74 plasmid (20 μg) , and pCMV-VSV-G plasmid (2 μg) ; after mixing, 105 μL PEI was added; after mixing, the transfection complex was let stand for 15 minutes in room temperature. The transfection complex was then added to 293T cells in 10 mL fresh serum-free medium, incubated in an incubator at 37℃, 5%CO ₂ for 6 hours. Cell medium was discarded. 20 mL fresh complete medium was added to 293T cells, then incubated in an incubator at 37℃, 5%CO ₂.3 days later, culture medium was collected and centrifuged at 1000 rpm, 4℃. The supernatant containing sgRNA ^iBAR library lentiviruses was collected, viral titer was measured, and aliquoted for future use.

2. Construction of Cas9 ⁺ sgRNA ^iBAR cancer cell library

HCT116 (human colon cancer cell line) , SW480 (human colorectal adenocarcinoma cell line) , and Caco2 (human colorectal adenocarcinoma cell line) were chosen for Cas9 ⁺ sgRNA ^iBAR cancer cell library construction and drug treatment.

2×10 ⁵ cancer cells from each cell line were seeded in 6-well plate and cultured in 37℃, 5%CO ₂ incubator. After 24 hours, 100 μL Cas9 packaged lentivirus was added into the cell medium, and cancer cells were cultured in 37℃, 5%CO ₂ incubator. After 24 hours, the medium was discarded, and fresh complete medium was added to the cancer cells. The cancer cells were allowed to grow for 7 days in 37℃, 5%CO ₂ incubator, then sorted with FACS using mCherry marker (carried on the Cas9-lentiviral vector) . The sorted cancer cells with mCherry fluorescence were Cas9 expressing (Cas9 ⁺) cells, and were expanded for Cas9 ⁺ sgRNA ^iBAR library construction.

In order to ensure at least 1000-fold sgRNA ^iBAR coverage in the Cas9 ⁺ sgRNA ^iBAR cancer cell library, sgRNA ^iBAR library lentivirus obtained above were added to 2×10 ⁷ Cas9 ⁺ cancer cells in medium (no antibiotics) at an MOI of 3 and gently mixed. Cas9 ⁺ cancer cells were cultured for 24 hours in a 37℃, 5%CO ₂ incubator for infection. The next day, the medium was discarded, fresh complete medium was added to the Cas9 ⁺ cancer cells, then cultured in a 37℃, 5%CO ₂ incubator. Cas9 ⁺ cancer cells were passaged every 3 days, in fresh complete medium supplemented with Puromycin. Cas9 ⁺ cancer cells not successfully transfected with sgRNA ^iBAR plasmids would die. After two to three consecutive passages, sgRNA ^iBAR cancer cell library was obtained (hereinafter also referred to as “Cas9 ⁺ sgRNA ^iBAR HCT116 library, ” “Cas9 ⁺sgRNA ^iBAR SW480 library, ” and “Cas9 ⁺ sgRNA ^iBAR Caco2 library” , respectively) .

3. Screening of Cas9 ⁺ sgRNA ^iBAR cancer cell library treated with anti-cancer drug

Before treating the Cas9 ⁺ sgRNA ^iBAR cancer cell library with DNA damaging agent (e.g., PARP inhibitor (PARPi) , or ATR inhibitor (ATRi) ) , drug toxicity curve was measured for each cancer cell line.

2000 HCT116 or SW480 or Caco2 cells were added per well in a 96-well plate, 100 μL medium was added per well, then incubated in a 37℃, 5%CO ₂ cell incubator. The next day, PARPi or ATRi of various concentrations was added to each well, 3 replicates for each concentration. The final PARPi concentrations 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 ATRi concentrations 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. After three doubling time with the presence of PARPi or ATRi,

Luminescent Cell Viability Assay (ATP assay) was conducted to obtain the drug toxicity curve. PARPi were tested on HCT116 and SW480 cell lines. ATRi were tested on HCT116 and Caco2 cell lines.

Based on the obtained drug toxicity curve for each cancer cell line, drug concentrations corresponding to cell growth inhibition of IC ₅₀-IC ₇₀ were chosen for Cas9 ⁺ sgRNA ^iBAR cancer cell library screening. For example, the concentration of PARPi was 5 μM for HCT116 and 10 μM for SW480. The concentration of ATRi was 0.08 μM for HCT116 and 0.1 μM for Caco2. 1×10 ⁶ Cas9 ⁺ sgRNA ^iBAR cancer cells were placed in a 150 mm cell culture dish and cultured in a 37℃, 5%CO ₂ cell incubator. The next day, Cas9 ⁺ sgRNA ^iBAR cancer cells were treated with PARPi or ATRi (test group) or DMSO (control group) . PARPi were tested on Cas9 ⁺ sgRNA ^iBAR HCT116 library and Cas9 ⁺ sgRNA ^iBAR SW480 library. ATRi were tested on Cas9 ⁺ sgRNA ^iBAR HCT116 library and Cas9 ⁺ sgRNA ^iBAR Caco2 library. Two biological replicates were set up for each group. Fresh cell medium (added with drug or DMSO) was changed every three days. The drug or control treatment continued, and cells were collected after treating for 9-10 doubling time or after treating for 15-16 doubling time (see FIG. 2) . For adherent cells, dead cells would be floating in the culture medium, hence adherent cells harvested by trypsinization were alive (or mostly alive) cells. During the entire screening process and cell collection process, the cell number was always at least about 1000-fold of the size of the sgRNA ^iBAR library for each replicate, i.e., at least about 1000 cells for each sgRNA ^iBAR.

4. Identification and analysis of target genes

Genomic DNA was extracted from post-treatment cancer cells collected above (mostly alive Cas9 ⁺ sgRNA ^iBAR cancer cells) . For each cancer cell type, there was a “9-10 PDT test group, ” a “15-16 PDT test group, ” a “9-10 PDT control group, ” and a “15-16 PDT control group” ; with two biological replicates for each group. For PARPi or ATRi, each anti-cancer drug were tested on two different cell line libraries. sgRNA ^iBAR encoding fragments were PCR amplified from the extracted genome, purified, and prepared for NGS sequencing. MAGeCK ^iBAR algorithm was used for sequencing data analysis (see Zhu et al., “Guide RNAs with embedded barcodes boost CRISPR-pooled screens, ” Genome Biol. 2019; 20: 20; the content of which is incorporated herein by reference in its entirety) , which contains three main parts: analysis preparation, statistical tests, and rank aggregation. Briefly, each sgRNA ^iBAR targeted gene was scored and ranked based on the enrichment or depletion degree of each gene between the test group and the control group, in order to determine if such gene was a candidate gene with high confidence. See FIG. 3 for target gene identification workflow. sgRNA ^iBAR encoding fragments would be depleted compared to control (negative screen) for candidate genes whose inactivation result in sensitive phenotype to anti-cancer drug killing; while sgRNA ^iBAR encoding fragments would be enriched compared to control (positive screen) for candidate genes whose inactivation result in resistant phenotype to anti-cancer drug killing. These top ranking candidates were found to be involved in cell proliferation, cell death, cell cycle regulation, or immune response.

5. Results

Compared to control, candidate genes whose sgRNA ^iBAR encoding fragments are depleted in the harvested alive cells in either “9-10 PDT test group” or “15-16 PDT test group” and in either cell line library (e.g., either Cas9 ⁺ sgRNA ^iBAR HCT116 library or Cas9 ⁺ sgRNA ^iBAR SW480 library for PARPi) with FDR≤0.1 were categorized as drug sensitive genes whose inactivation makes the cancer cells sensitive to the anti-cancer drug. Exemplary drug sensitive genes of PARPi are shown in Tables 3, A, 9, and 10. Exemplary drug sensitive genes of ATRi are shown in Table 4.

Compared to control, candidate genes whose sgRNA ^iBAR encoding fragments are enriched in the harvested alive cells in either “9-10 PDT test group” or “15-16 PDT test group” and in either cell line library with FDR≤0.1 were categorized as drug resistant genes whose inactivation makes the cancer cells resistant to the anti-cancer drug. Exemplary drug resistant genes of PARPi are shown in Tables 7, B, 9, and 10. Exemplary drug resistant genes of ATRi are shown in Table 8.

A subset of PARPi sensitive and resistant genes identified in “15-16 PDT test group” and in either Cas9 ⁺ sgRNA ^iBAR HCT116 library or Cas9 ⁺ sgRNA ^iBAR SW480 library for PARPi with screening scores (reflecting the significance and extent of enrichment/depletion) and FDRs (reflecting significance) are shown in Table 9.

Table 9. Drug sensitive or resistant genes of PARPi

Results obtained here, particularly genes whose inactivation were found to confer cancer cell sensitivity to anti-cancer drug (e.g., PARPi or ATRi) killing, demonstrate valuable targets in cancer therapy as well as biomarkers for patient selection. Drug resistant genes whose inactivation make cancer cells resistant to anti-cancer drug (s) would serve as biomarkers for not selecting such patients, and/or that alternative cancer therapeutic agent (s) should be used.

6. Target gene verification

To verify the identified drug sensitive genes and drug resistant genes, a subset of genes were selected from PARPi sensitive genes and PARPi resistant genes (see Table 10) for experimental testing.

Briefly, nucleic acids encoding the sgRNAs targeting these genes were designed and synthesized. The forward strand and the reverse strand were allowed to anneal to form double-stranded nucleic acid with over-hangs on both ends. The lentiviral sgRNA-expressing backbone modified in house based on pLenti-sgRNA-Lib (addgene #53121) was enzymatically cleaved, the double-stranded nucleic acid was ligated into the cleavage site, to obtain sgRNA plasmids. This sgRNA plasmid carrys puromycin and ampicillin antibiotic genes.

To amplify sgRNA plasmids, 2 μL sgRNA plasmid was added to 20 μL competent cells (E.coli) in a 1.5 mL Eppendorf tube, followed by standard ice/heat-shock transformation protocol, let grow in liquid LB in 37℃ shaker for 1 hour, then spread onto an LB ^Amp+ plate and let grow overnight at 37℃. The next day, 5-10 single clones were picked for growth overnight in LB ^Amp+ liquid medium in 37℃ shaker. The following day, sgRNA plasmids were extracted with kit, then sequenced to verify sequences.

sgRNA lentiviruses were then obtained using standard protocol. Briefly, 5×10 ⁶ 293T cells were placed in a 10 cm cell culture dish and cultured overnight in a 37℃, 5%CO ₂ incubator. The next day, culture medium was discarded, fresh serum-free medium was added to the 293T cells. The transfection complex was prepared using serum-free medium (1 mL) , sgRNA plasmid purified above (10 μg) , pCMVR8.74 plasmid (10 μg) , and pCMV-VSV-G plasmid (1 μg) ; after mixing, 52.5 μL PEI was added. After mixing, the transfection complex was let stand for 15 minutes in room temperature. The transfection complex was then added to 293T cells in fresh serum-free medium, incubated in an incubator at 37℃, 5%CO ₂ for 6-8 hours. Cell medium was discarded, fresh complete medium was added to 293T cells, then incubated in an incubator at 37℃, 5%CO ₂.72 hours later, the cell culture was collected and centrifuged at 200 g, 5 minutes. The supernatant containing sgRNA lentiviruses was collected, filtered with a 0.45 μm filter, then stored at -80℃ for later use.

To construct cancer cell line with target gene KO, 2×10 ⁵ SW620 cancer cells were seeded in 6-well plate and cultured in 37℃, 5%CO ₂ incubator. After 24 hours, 100 μL Cas9 packaged lentivirus was added into the cell medium, and cancer cells were cultured in 37℃, 5%CO ₂ incubator. After 24 hours, the medium was discarded, and fresh complete medium was added to the cancer cells. The cancer cells were allowed to grow for 7 days in 37℃, 5%CO ₂ incubator, then sorted with FACS using mCherry marker (carried on the Cas9-lentiviral vector) . The sorted cancer cells with mCherry fluorescence were Cas9 expressing (Cas9 ⁺) cells, and were expanded for Cas9 ⁺ sgRNA construction. 500 μL non-concentrated sgRNA lentiviruses obtained above were added to 2×10 ⁷ Cas9 ⁺ cancer cells in medium (no antibiotics) at an MOI of 3 and gently mixed. Cas9 ⁺ cancer cells were cultured overnight in a 37℃, 5%CO ₂ incubator for infection. The next day, the medium was discarded, fresh complete medium was added to the Cas9 ⁺ cancer cells, then cultured in a 37℃, 5%CO ₂ incubator for 48 hours. Then 1μL puromycin was added to the culture medium for selection. Cas9 ⁺ cancer cells not successfully transfected with sgRNA plasmids would die.

To test target gene KO efficiency (%) , a subset of cancer cells treated with puromycin from above were collected. Genomic DNA was extracted, and target gene sequence was amplified and sequenced. KO efficiency was calculated by Tracking of Indels by Decomposition (TIDE) web tool, which can accurately reconstructs the spectrum of indels from the sequence traces, and reporting the detected indels and their frequencies as KO efficiency. Results are summarized in Table 10.

To test the response of the target gene KO-cancer cells to PARPi treatment, 1000 cancer cells for each target gene KO were placed into a 96-well plate, culture medium was added per well, then incubated in a 37℃, 5%CO ₂ cell incubator overnight. The next day, PARPi of various concentrations was prepared at 1: 3 dilution, then added to each well, 3 replicates for each concentration. The final PARPi concentrations 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 control set of experiments was conducted with cancer cells not carrying any of the target gene KOs ( “WT cancer cells” ) , cultured and treated with PARPi under the same condition. After 2-3 doubling time with the presence of PARPi, CellTiter-

Luminescent Cell Viability Assay (ATP assay) was conducted to obtain the drug toxicity curve (see FIG. 4) . IC50 results are shown in Table 10.

Table 10. Verification of drug sensitive genes and drug resistant genes of PARPi

As shown in FIG. 4 and Table 10, the screening identified drug sensitive genes after KO indeed conferred sensitivity to PARPi killing in cancer cells (e.g., see ATM, BRCA1, WEE1, etc. ) , and the screening identified drug resistant genes after KO conferred resistance to PARPi killing in cancer cells (e.g., see PARP1, MYC) . Further, the IC50 fold change between target gene KO and WT cancer cells largely followed screening results: highly enriched or depleted target genes from the screen (e.g., with higher screen score, e.g., see Table 9) also showed greater difference in IC50.

These target gene verification results demonstrate that the screening method described herein is effective in obtaining drug sensitive genes and/or drug resistant genes, and that the drug sensitive genes and drug resistant genes provided herein are of high accuracy and will be of great value in cancer diagnostics and therapy.

7. Discussion

The above method can be used in drug sensitive gene and/or drug resistant gene screening for any anti-cancer drugs (such as drugs targeting different pathways or the same pathway) and any cancer types. The obtained drug sensitive genes and/or drug resistant genes have significant implications in cancer therapy, patient selection, and new drug screening or design.

For example, if the diagnosis of a cancer patient indicates that for a single pathway (e.g., targeted by PARPi, etc. ) : 1) the patient only has inactivate mutation in target gene (s) whose inactivation confers sensitivity to pathway-targeting drug (s) , then this patient is a perfect candidate for treatment with such drug (s) ; 2) the patient only has inactivate mutation in target gene (s) whose inactivation confers resistance to pathway-targeting drug (s) , then this patient may not be suitable for treatment with drug (s) targeting such pathway, and alternative treatment methods should be sought; 3) the patient has inactivate mutation in both target gene (s) whose inactivation confers resistance to pathway-targeting drug (s) , and target gene (s) whose inactivation confers sensitivity to pathway-targeting drug (s) , then more analysis needs to be conducted, e.g., if the drug sensitivity is sufficient to help kill cancer cells before drug resistance occurs, if genes conferring drug resistance are of less significance in cancer development compared to those that confer drug sensitivity, whether one pathway-targeting drug should be selected over the other pathway-targeting drug, whether one drug should be used before the other or used together, whether alternative treatment method exists, etc. The composite score of drug sensitive aberrations and drug resistant aberrations described herein (e.g., Formula I) may also contribute to the treatment decision.

Target genes obtained for multiple anti-cancer drugs, such as anti-cancer drugs targeting the same or different pathways involved in cancer development (e.g., PARPi and ATRi, both related to DNA damaging but targeting different pathways) , can be combined or overlapped to find common target genes. Gene functions and/or mechanisms of action can be further analyzed to make treatment decision, and/or for drug design/development. For example, if a patient carries inactivate mutation in a gene whose inactivation confers sensitivity to drugs X, Y, and Z, then a combination therapy with drugs X, Y, and Z might confer synergistic anti-cancer activity. For example, if a patient carries inactivate mutations in different genes (of the same pathway or different pathways) whose inactivation confers sensitivity to drugs X, Y, and Z, then a combination therapy with drugs X, Y, and Z might confer synergistic anti-cancer activity. For another example, if a new drug can be designed to target various pathways involving target genes whose deletion confer sensitivity to known drugs, then the obtained new drug might have superior therapeutic effect compared to known drugs.

As an example, for various pathways targeted by, e.g., PARPi, ATRi, other drugs for treating colorectal cancer, or other drugs for treating other cancer types but not yet tested/developed for colorectal cancer treatment, etc., if a patient is diagnosed that the patient 1) has inactivate mutations in shared target gene (s) (or different genes with shared pathways) whose inactivation confers sensitivity to various pathway-targeting drugs, then a single or preferably a combination therapy with such drugs can be used for cancer treatment; 2) has inactivate mutation in shared target gene (s) (or different genes with shared pathways) whose inactivation confers resistance to various pathway-targeting drugs, then alternative treatment methods should be sought, or further analysis on gene function and/or mechanism of action should be conducted to determine if combination therapy (e.g., one used before the other) using such pathway-targeting drugs may alleviate the drug resistance phenotype. For example, drug X that will experience drug resistance from the target gene mutation later during treatment can be used first, and a drug Y that will experience drug resistance from the target gene mutation early on but may be sufficiently effective can be used only at the beginning or throughout the process, in combination with drug X.

Example 2: Composite score correctly reflects cancer killing efficacy by anti-cancer drug

This Example provides evidence that composite score calculated using methods described herein (e.g., Formula I) based on drug sensitive genes and drug resistant genes of anti-cancer agent (e.g., DNA damaging agents such as PARPi or ATRi) identified using screening methods described herein correctly reflects/can predict cancer killing efficacy by the corresponding anti-cancer agent.

1. Random selection of colorectal cancer samples for composite score calculation

A collection of colorectal cancer cell lines and patient-derived xenografts (PDXs) was tested for response to PARPi treatment, by measuring cell viability rate (reflected as IC50) or PDX growth inhibition rate following standard methods (also see Example 1) . 16 cancer samples (10 PDXs and 6 cancer cell lines; see FIG. 5A) were selected based on various response against PARPi treatment, for use in composite score calculation. Their corresponding cell viability response or PDX growth inhibition response is reflected as “drug response” in FIG. 5C.

2. Detection, filtration, and annotation of mutations in selected cancer samples

Above selected 16 cancer samples were individually sequenced by NGS. For each sample, mutations were detected from the sequencing data. The raw mutation sites were further filtered according to mutation quality to remove low confidence mutation sites. The remaining high-quality mutation sites were mapped to corresponding genes, and annotated for the impact of the mutation on the corresponding gene function based on database. Only mutation sites with deleterious impact to corresponding genes were retained for subsequent analysis.

3. Gene-level functional annotation and series of database information integration for further filtration

The remaining mutation sites from above were then annotated based on prevalence, clinical significance, curated impact, gene ontology, and pathway information etc. from both external and internal database sources. Low-clinical impact mutations were further filtered out. Then overall loss-of-function (LOF) probability was calculated for each gene mapped to the remaining mutations for each sample.

4. Composite score calculation

To calculate composite score for each cancer sample and test its accuracy for predicting PARPi treatment response, a total of 51 PARPi sensitive genes and PARPi resistant genes, obtained from and/or verified in Example 1 and with at least one high confidence deleterious mutation in any of the 16 selected cancer samples after filtration, were selected ( “test gene panel” ) . Their corresponding LOF probability is shown in FIG. 5A. For each cancer sample, the gene-level LOF probability across the 51 PARPi sensitive/resistant genes was used to calculate the

portion in Formula I. Gene-level contribution and pathway-level contribution of mutations detected in the “test gene panel” to PARPi treatment were quantified by integrating the corresponding weight

coefficient of correlation of each gene (r _i) , and pre-calculated weight for the related pathways in PARPi response

to calculate the raw composite score. The raw composite score was further adjusted and scaled accordingly to the sample types (i.e., cell line, PDX, patient) to generate the final composite score for each cancer sample (see FIGs. 5B and 5C “composite score” row) .

5. Results and conclusion

As can be seen from FIGs. 5B and 5C, when the composite score of the cancer sample according to Formula I was above 0, the cancer sample indeed showed sensitivity to PARPi killing; while when the composite score of the cancer sample according to Formula I was below 0, the cancer sample indeed showed resistance to PARPi killing. Further, the higher the absolute value of the composite score, the better the prediction power of actual PARPi response for that cancer sample (see “prediction” row based on composite score in FIG. 5C) . For example, for cancer samples with a composite score of above 0.1, the prediction is “true” for the sample’s actual sensitivity to PARPi killing (see PDX3, PDX6, PDX10, cell line 1, cell line 2, and cell line 6) . For cancer samples with a smaller negative composite score (bigger absolute value of the composite score) , the prediction is “true” for the sample’s actual resistance to PARPi killing (see PDX8, cell line 4, cell line 4) . No actually tested-sensitive cancer sample received a composite score of below 0 according to Formula I, demonstrating the great prediction power of “true positives” of methods described herein. One actually tested-sensitive cancer sample, cell line 3, received a composite score of 0. All actually tested-resistant cancer samples received a composite score of below or equal to 0 according to Formula I (demonstrating the great prediction power of “true positives” of methods described herein) , with the exception of PDX9, which had a composite score of 0.011. Hence, 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 treatment based on composite score was “ambiguous. ” More evaluation may be needed to identify false positives and false negatives based on the prediction of the composite score.

These findings demonstrate that drug sensitive genes and drug resistant genes of anti-cancer agents (e.g., DNA damaging agents such as PARPi or ATRi) identified using screening methods described herein, and composite scores obtained based on them using methods described herein, correctly reflect/can predict cancer killing efficacy by the corresponding anti-cancer agent, and can serve as tools for cancer diagnosis, treatment selection, and/or patient selection. For example, when the composite score of the patient according to Formula I is above 0, the patient may be suitable for (i.e., may benefit from) the anti-cancer drug (e.g., DNA damaging agent such as PARPi or ATRi) treatment. If the composite score of the patient according to Formula I is above or equal to at least 0.1 (e.g., 0.3) , the patient can be selected or recommended for the anti-cancer drug treatment. If the composite score of the patient according to Formula I is more than 0 but less than 0.1, the patient may be suitable for the anti-cancer drug treatment, but should be further evaluated using other method (s) (e.g., drug dosage test, cancer genetic testing (e.g., look for additional synergistic mutations that may contribute to the anti-cancer drug treatment, or verify the primary cancer type) , etc. ) or based on other information (e.g., patient’s clinical record or known drug resistance, etc. ) to determine whether the patient should be selected or recommended for the anti-cancer drug treatment. If the composite score of the patient according to Formula I is below or equal to 0, the patient may not be suitable for (i.e., may not benefit from) or should be excluded from the anti-cancer drug treatment. Further evaluation using other method (s) or or based on other information described herein may be needed if the composite score of the patient according to Formula I is equal to 0, or very close to 0 (e.g., -0.1 to 0) , before completely ruling out the patient from receiving the anti-cancer drug treatment.

Claims

A method of treating a 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 on the basis of having one or more drug sensitive aberrations in one or a plurality of drug sensitive 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 in a sample from the individual.
The method of claim 1, wherein the individual is selected for treatment on the basis of having a composite score of drug sensitive aberrations and drug resistant aberration above a threshold level in the sample from the individual, wherein the drug resistant aberration is one or more drug resistant aberrations in one or a plurality of drug resistant 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.
The method of claim 1 or 2, further comprising acquiring knowledge of one or more drug sensitive aberrations in one or a plurality of drug sensitive 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 one or more drug resistant aberrations in one or a plurality of drug resistant 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 in the sample from the individual prior to the administration of the DNA damaging agent.
The method of claim 3, wherein the acquisition of knowledge comprises obtaining a composite score of drug sensitive aberrations and drug resistant aberration in the sample of the individual.
The method of claim 3 or 4, wherein the acquiring knowledge of one or more drug sensitive aberrations and/or one or more drug resistant aberrations comprises detecting the one or more drug sensitive aberrations in one or a plurality of drug sensitive 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 the one or more drug resistant aberrations in one or a plurality of drug resistant 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 in the sample.
A method of identifying an individual having a colorectal cancer who may benefit from a treatment comprising administration of a DNA damaging agent, the method comprising detecting in a sample from the individual one or more drug sensitive aberrations in one or a plurality of drug sensitive 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 the one or more drug sensitive aberrations in the sample identifies the individual as one who may benefit from the treatment.
The method of claim 6, wherein the method comprises detecting in a sample from the individual one or more drug sensitive aberrations in one or a plurality of drug sensitive 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 resistant aberrations in one or a plurality of drug resistant 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, wherein a composite score of the drug sensitive aberrations and drug resistant aberrations above a threshold level identifies the individual as one who may benefit from the treatment.
The method of any one of claims 5-7, wherein the detecting of the one or more drug sensitive aberrations in one or a plurality of drug sensitive genes and/or one or more drug resistant aberrations in one or a plurality of drug resistant genes comprise sequencing the plurality of drug sensitive genes and/or drug resistant genes, or a relevant portion thereof.
The method of any one of claims 1-8, wherein the DNA damaging agent is a PARPi or an ATRi.
The method of claim 9, wherein the DNA damaging agent is a PARPi.
The method of claim 10, wherein the one or a plurality of drug sensitive genes is 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.
The method of claim 10 or 11, wherein the one or a plurality of drug sensitive genes is 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.
The method of any one of claims 10-12, wherein the one or a plurality of drug resistant genes is 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.
The method of any one of claims 10-13, wherein the one or a plurality of drug resistant genes is 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.
The method of claim 9, wherein the DNA damaging agent is an ATRi.
The method of claim 15, wherein the one or a plurality of drug sensitive genes is 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.
The method of claim 15 or 16, wherein the one or a plurality of drug resistant genes is 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.
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, II, III, or IV colon cancer, a colon cancer characterized with a genomic instability, or a colon cancer characterized with an alteration of a pathway.
The method of any one of claims 1-18, wherein the individual has previously undergone a therapy.
The method of any one of claims 1-19, wherein the sample is a tumor biopsy sample, a circulating tumor cell sample, or a fixed tissue sample.
The method of any one of claims 1-20, wherein the sample is selectively enriched for nucleic acids comprising, or polypeptides encoded by, one or a plurality of drug sensitive genes and/or one or a plurality of drug resistant genes prior to the aberration analysis.
The method of any one of claims 1-21, wherein the one or more drug sensitive aberrations and/or the one or more drug resistant aberrations comprise one or more of an insertion, deletion or substitution of one or more nucleotides, a genomic rearrangement, an alteration in a promoter, a gene fusion, or a copy number alteration.
The method of any one of claims 1-22, wherein the individual is a human.
A plurality of capture nucleic acid molecules configured to hybridize to a plurality of drug sensitive 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 a plurality of drug resistant 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.
The plurality of capture nucleic acid molecules of claim 24, wherein each of the plurality of the capture nucleic acid molecules comprises between about 10 and about 200 nucleotides.
The plurality of capture nucleic acid molecules of claim 24 or 25, wherein each of the plurality of the capture nucleic acid molecules are conjugated to an affinity reagent or a detection reagent.
The plurality of capture nucleic acid molecules of any one of claims 24-26, wherein the plurality of capture nucleic acid molecules are configured to hybridize to a plurality of drug sensitive 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 plurality of drug resistant 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.
The plurality of capture nucleic acid molecules of any one of claims 24-27, wherein the plurality of capture nucleic acid molecules are configured to hybridize to a plurality of drug sensitive 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 a plurality of drug resistant 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.
The plurality of capture nucleic acid molecules of any one of claims 24-26, wherein the plurality of capture nucleic acid molecules are configured to hybridize to a plurality of drug sensitive 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 a plurality of drug resistant 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.
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 or polypeptides, wherein the one or more nucleic acids or polypeptides are derived from a sample obtained from an individual having a colorectal cancer; (b) analyze the plurality of sequence reads for the presence of one or more drug sensitive aberrations in one or a plurality of drug sensitive 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 one or more drug resistant aberrations in one or a plurality of drug resistant 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, based on the analyzing, one or more drug sensitive aberrations in one or a plurality of drug sensitive 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 one or more drug resistant aberrations in one or a plurality of drug resistant 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 .
A non-transitory computer readable storage medium comprising one or more programs executable by one or more computer processors of the system of claim 30.
The system of claim 30 or the non-transitory computer readable storage medium of claim 31, wherein the one or more drug sensitive aberrations is in one or a plurality of drug sensitive 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 the one or more drug resistant aberrations is in one or a plurality of drug resistant 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.
The system of claim 30 or 32 or the non-transitory computer readable storage medium of claim 31 or 32, wherein the one or more drug sensitive aberrations is in one or a plurality of drug sensitive 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 the one or more drug resistant aberrations is in one or a plurality of drug resistant 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.
The system of claim 30 or the non-transitory computer readable storage medium of claim 31, wherein the one or more drug sensitive aberrations is in one or a plurality of drug sensitive 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 the one or more drug resistant aberrations is in one or a plurality of drug resistant 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.