JP2016510591A5 - - Google Patents
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- JP2016510591A5 JP2016510591A5 JP2015559038A JP2015559038A JP2016510591A5 JP 2016510591 A5 JP2016510591 A5 JP 2016510591A5 JP 2015559038 A JP2015559038 A JP 2015559038A JP 2015559038 A JP2015559038 A JP 2015559038A JP 2016510591 A5 JP2016510591 A5 JP 2016510591A5
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- JP
- Japan
- Prior art keywords
- cancer
- mutation
- inhibitor
- detecting
- akt
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 230000035772 mutation Effects 0.000 claims 15
- 201000011510 cancer Diseases 0.000 claims 14
- 210000004027 cells Anatomy 0.000 claims 8
- 239000003197 protein kinase b inhibitor Substances 0.000 claims 8
- 230000014509 gene expression Effects 0.000 claims 5
- 239000003112 inhibitor Substances 0.000 claims 5
- 230000002401 inhibitory effect Effects 0.000 claims 5
- 101700006234 AKT1 Proteins 0.000 claims 4
- 102100001248 AKT1 Human genes 0.000 claims 4
- 102000010400 1-phosphatidylinositol-3-kinase activity proteins Human genes 0.000 claims 3
- 108040005185 1-phosphatidylinositol-3-kinase activity proteins Proteins 0.000 claims 3
- 101710031851 AKT1S1 Proteins 0.000 claims 3
- 102100017507 AKT1S1 Human genes 0.000 claims 3
- 101700006583 AKT2 Proteins 0.000 claims 3
- 101700004058 AKT3 Proteins 0.000 claims 3
- 102100006725 AKT3 Human genes 0.000 claims 3
- 108020004999 Messenger RNA Proteins 0.000 claims 3
- 229920002106 messenger RNA Polymers 0.000 claims 3
- 208000005443 Circulating Neoplastic Cells Diseases 0.000 claims 2
- 108020004705 Codon Proteins 0.000 claims 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims 2
- 230000003281 allosteric Effects 0.000 claims 2
- 230000003321 amplification Effects 0.000 claims 2
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims 2
- 238000003199 nucleic acid amplification method Methods 0.000 claims 2
- 230000002018 overexpression Effects 0.000 claims 2
- 230000001225 therapeutic Effects 0.000 claims 2
- YOVVNQKCSKSHKT-HNNXBMFYSA-N (2S)-1-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-hydroxypropan-1-one Chemical compound C1CN(C(=O)[C@@H](O)C)CCN1CC1=C(C)C2=NC(C=3C=NC(N)=NC=3)=NC(N3CCOCC3)=C2S1 YOVVNQKCSKSHKT-HNNXBMFYSA-N 0.000 claims 1
- GRZXWCHAXNAUHY-NSISKUIASA-N (2S)-2-(4-chlorophenyl)-1-[4-[(5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl]piperazin-1-yl]-3-(propan-2-ylamino)propan-1-one Chemical group C1([C@H](C(=O)N2CCN(CC2)C=2C=3[C@H](C)C[C@@H](O)C=3N=CN=2)CNC(C)C)=CC=C(Cl)C=C1 GRZXWCHAXNAUHY-NSISKUIASA-N 0.000 claims 1
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical group C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 claims 1
- 101710042656 BQ2027_MB1231C Proteins 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 206010009944 Colon cancer Diseases 0.000 claims 1
- 206010014733 Endometrial cancer Diseases 0.000 claims 1
- 206010017758 Gastric cancer Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 206010025650 Malignant melanoma Diseases 0.000 claims 1
- 206010027406 Mesothelioma Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 208000008443 Pancreatic Carcinoma Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 206010038389 Renal cancer Diseases 0.000 claims 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N Sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 1
- 230000002860 competitive Effects 0.000 claims 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 201000010982 kidney cancer Diseases 0.000 claims 1
- 201000005202 lung cancer Diseases 0.000 claims 1
- 201000001441 melanoma Diseases 0.000 claims 1
- 238000002493 microarray Methods 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- LHNIIDJUOCFXAP-UHFFFAOYSA-N pictrelisib Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 LHNIIDJUOCFXAP-UHFFFAOYSA-N 0.000 claims 1
- 238000003753 real-time PCR Methods 0.000 claims 1
- 229960002930 sirolimus Drugs 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
Claims (27)
- ＡＫＴ１又はＰＲＡＳ４０変異を含むがん細胞の変異の存在を検出することを含む、がん細胞におけるＡＫＴ阻害剤の治療効果に対する耐性を検出するための方法であって、変異の存在は、がん細胞がＡＫＴ阻害剤に耐性になったか又は耐性になるであろうことを示している、方法。
- 変異の存在が、ＡＫＴ阻害剤を用いた治療後に検出される、請求項１に記載の方法。
- ＡＫＴ１変異がＷ８０を含む、請求項１又は２に記載の方法。
- Ｗ８０変異がシステイン残基の変化を含む、請求項１から３の何れか一項に記載の方法。
- ＡＫＴ３の発現レベルを検出することを更に含む、請求項１から４の何れか一項に記載の方法。
- ＡＫＴ３の過剰発現を検出することを更に含む、請求項１から５の何れか一項に記載の方法。
- ＡＫＴ阻害剤がアロステリック阻害剤である、請求項１から６の何れか一項に記載の方法。
- アロステリック阻害剤がＭＫ−２２０６である、請求項１から７の何れか一項に記載の方法。
- ＰＲＡＳ４０変異が停止コドンを含む、請求項１又２に記載の方法。
- 変異が１７８停止コドンを含む、請求項１、２及び９の何れか一項に記載の方法。
- ＡＫＴ阻害剤がＡＴＰ競合的阻害剤である、請求項１、２、９及び１０の何れか一項に記載の方法。
- ＡＫＴ阻害剤がＧＤＣ−００６８又はＧＳＫ２１１０１８３である、請求項１、２及び９から１１の何れか一項に記載の方法。
- ＡＫＴ３発現レベルがｍＲＮＡ発現レベルである、請求項１から１２の何れか一項に記載の方法。
- ｍＲＮＡ発現レベルがマイクロアレイ又はｑＲＴ−ＰＣＲを用いて測定される、請求項１から１３の何れか一項に記載の方法。
- ｍＲＮＡ発現レベルの変化が増加である、請求項１から１４の何れか一項に記載の方法。
- がんが、中皮腫、子宮内膜がん、膵臓がん、乳がん、肺がん、卵巣がん、前立腺がん、黒色腫、胃がん、結腸がん、腎臓がん、頭頸部がん、及びグリオーマからなる群から選択される、請求項１から１５の何れか一項に記載の方法。
- がんがＰＴＥＮ変異と関連している、請求項１から１６の何れか一項に記載の方法。
- がんがＰＴＥＮが低いか又はゼロの状態と関連している、請求項１から１７の何れか一項に記載の方法。
- がんがＡＫＴ変異、過剰発現又は増幅と関連している、請求項１から１８に記載の方法。
- がんがＰＩ３Ｋ変異と関連している、請求項１から１９の何れか一項に記載の方法。
- がんがＨｅｒ２／ＥｒｂＢ２増幅と関連している、請求項１から２０の何れか一項に記載の方法。
- がん細胞が循環腫瘍細胞（ＣＴＣ）である、請求項１から２１の何れか一項に記載の方法。
- 検出がｐＣＲにより変異を検出することを更に含む、請求項１から２２の何れか一項に記載の方法。
- がん細胞におけるＡＫＴ阻害剤の治療効果に対する耐性を検出するためのキットであって、ＡＫＴ１又はＰＲＡＳ４０変異を含むがん細胞の変異の存在を検出するための手段を含み、変異の存在は、がん細胞がＡＫＴ阻害剤に耐性になったか又は耐性になるであろうことを示している、キット。
- がん細胞に、ＰＩ３Ｋ阻害剤又はｍＴＯＲ阻害剤の有効量が投与される、請求項２４に記載のキット。
- ＧＤＣ−０９４１及びＧＤＣ−０９８０から選択されるＰＩ３Ｋ阻害剤の有効量が投与される、請求項２４又は２５に記載のキット。
- ラパマイシンから選択されるｍＴＯＲ阻害剤の有効量が投与される、請求項２４又は２５に記載のキット。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361769108P | 2013-02-25 | 2013-02-25 | |
| US61/769,108 | 2013-02-25 | ||
| PCT/US2014/017948 WO2014130923A2 (en) | 2013-02-25 | 2014-02-24 | Methods and compositions for detecting and treating drug resistant akt mutant |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019088252A Division JP2019176858A (ja) | 2013-02-25 | 2019-05-08 | 薬物耐性ａｋｔ変異体を検出し治療するための方法及び組成物 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016510591A JP2016510591A (ja) | 2016-04-11 |
| JP2016510591A5 true JP2016510591A5 (ja) | 2017-03-30 |
| JP6669500B2 JP6669500B2 (ja) | 2020-03-18 |
Family
ID=50290260
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015559038A Active JP6669500B2 (ja) | 2013-02-25 | 2014-02-24 | 薬物耐性ａｋｔ変異体を検出し治療するための方法及び組成物 |
| JP2019088252A Pending JP2019176858A (ja) | 2013-02-25 | 2019-05-08 | 薬物耐性ａｋｔ変異体を検出し治療するための方法及び組成物 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019088252A Pending JP2019176858A (ja) | 2013-02-25 | 2019-05-08 | 薬物耐性ａｋｔ変異体を検出し治療するための方法及び組成物 |
Country Status (11)
| Country | Link |
|---|---|
| US (2) | US9994913B2 (ja) |
| EP (1) | EP2959014B1 (ja) |
| JP (2) | JP6669500B2 (ja) |
| KR (1) | KR102182488B1 (ja) |
| CN (1) | CN105247072B (ja) |
| AR (1) | AR094873A1 (ja) |
| BR (1) | BR112015020054A2 (ja) |
| CA (1) | CA2901126C (ja) |
| MX (1) | MX369175B (ja) |
| RU (1) | RU2015140573A (ja) |
| WO (1) | WO2014130923A2 (ja) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105247072B (zh) | 2013-02-25 | 2019-10-15 | 基因泰克公司 | 检测和治疗抗药性akt突变体的方法和组合物 |
| EP3162156B1 (en) | 2014-06-27 | 2020-04-22 | Techflux Inc. | Method and device for transmitting data unit |
| CN107921026A (zh) * | 2015-08-28 | 2018-04-17 | 诺华股份有限公司 | 药物组合物包含(a)α‑同种型特异性PI3K抑制剂alpelisib(BYL719)和(b)AKT抑制剂,优选MK‑2206,afuresertib或uprosertib及其在治疗/预防癌症中的应用 |
| US20180325902A1 (en) * | 2015-11-06 | 2018-11-15 | The Penn State Research Foundation | Compositions and methods relating to cancer |
| US11626275B2 (en) * | 2018-08-13 | 2023-04-11 | Thermo Fisher Scientific (Bremen) Gmbh | Isotopic mass spectrometer |
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| WO2005113762A1 (en) | 2004-05-18 | 2005-12-01 | Pfizer Products Inc. | CRYSTAL STRUCTURE OF PROTEIN KINASE B-α (AKT-1) AND USES THEREOF |
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| US8063050B2 (en) | 2006-07-06 | 2011-11-22 | Array Biopharma Inc. | Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors |
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| EP2247756A2 (en) * | 2008-02-21 | 2010-11-10 | Université Libre de Bruxelles | Method and kit for the detection of genes associated with pik3ca mutation and involved in pi3k/akt pathway activation in the er-positive and her2-positive subtypes with clinical implications |
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| CA2894153A1 (en) * | 2012-12-07 | 2014-06-12 | The General Hospital Corporation | Combinations of a pi3k/akt inhibitor compound with an her3/egfr inhibitor compound and use thereof in the treatment of a hyperproliferative disorder |
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