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Profile Name | APC inact mut |
Gene Variant Detail | |
Relevant Treatment Approaches | CTNNB1 Inhibitor Tankyrase Inhibitor |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
APC inact mut | colon cancer | sensitive | Sirolimus | Preclinical | Actionable | In preclinical trials, Sirolimus (rapamycin) was shown effective in reducing tumors in mouse models of familial adenomatous polyposis and colon cancer with APC deficient tumors (PMID: 18768809, PMID: 20080688). | 18768809 20080688 | |
APC inact mut | colon cancer | sensitive | Vinorelbine | Preclinical | Actionable | In preclinical studies, cells deficient in Apc protein had increased sensitivity to Navelbine (vinorelbine) compared to wild-type cells, and Navelbine (vinorelbine) treament decreased adenoma size in an Apc-deficient mouse model (PMID: 22399804). | 22399804 | |
APC inact mut | colon cancer | sensitive | Vandetanib | Preclinical | Actionable | In a preclinical study, Caprelsa (vandetanib) reduced the number of dextran sodium sulfate-induced tumors in an APC-deficient mouse model for colon cancer (PMID: 20811697). | 20811697 | |
APC inact mut | colorectal cancer | sensitive | Celecoxib + Erlotinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Celebra (celecoxib), in combination with Tarceva (erlotinib), demonstrated efficacy in reducing tumor number and volume in APC inactivating mutant mice and in human colorectal cancer cell line xenograft models (PMID: 17909047). | 17909047 | |
APC inact mut | colorectal cancer | sensitive | Celecoxib | Preclinical | Actionable | In a preclinical study, APC inactivating mutant mouse models of colon cancer had reduced polyp formation after treatment with Celebra (celecoxib) (PMID: 17909047). | 17909047 | |
APC inact mut | colorectal cancer | sensitive | Sulindac | Preclinical | Actionable | In a preclinical study, colorectal cancer mouse models carrying APC inactivating mutations had reduced intestinal tumor burden after treatment with Clinoril (sulindac) (PMID: 19755659). | 19755659 | |
APC inact mut | colorectal cancer | sensitive | Erlotinib + Ibuprofen | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ibuprofen, in combination with Tarceva (erlotinib), demonstrated efficacy in reducing tumor number and volume in APC inactivating mutant mice and in cell line xenograft models of colorectal cancer (PMID: 17909047). | 17909047 | |
APC inact mut | colorectal cancer | sensitive | Dasatinib | Preclinical | Actionable | In a preclinical study, the combination of Sprycel (dasatinib) and curcumin inhibited tumor growth in a mouse model of colorectal cancer harboring an Apc mutation (PMID: 20473900). | 20473900 | |
APC inact mut | colon cancer | sensitive | CTNNB1 Inhibitor | CGP049090 | Preclinical | Actionable | In a preclinical study, CGP049090 inhibited proliferation of a colorectal cancer cell line harboring an APC inactivating mutation in culture (PMID: 14749129). | 14749129 |
APC inact mut | colon cancer | sensitive | CTNNB1 Inhibitor | ICG-001 | Preclinical | Actionable | In a preclinical study, ICG-001 decreased cell proliferation in colon cancer cell lines and in mouse models carrying APC inactivating mutations (PMID: 15314234). | 15314234 |
APC inact mut | colon cancer | sensitive | MF tricyclic | Preclinical | Actionable | In a preclinical study, mouse models of colon cancer carrying an APC 716del mutation had reduced polyp formation after treatment with MF tricyclic (PMID: 23843721). | 23843721 | |
APC inact mut | colon cancer | sensitive | CTNNB1 Inhibitor | PKF115-584 | Preclinical | Actionable | In a preclinical study, PKF115-584 inhibited proliferation of colorectal cancer cell line harboring an APC inactivating mutation in culture (PMID: 14749129). | 14749129 |
APC inact mut | colon cancer | sensitive | CTNNB1 Inhibitor | StAx-35 | Preclinical | Actionable | In a preclinical study, StAx-35 inhibited proliferation of colon cancer cell lines carrying APC deletions in culture (PMID: 23071338). | 23071338 |
APC inact mut | colorectal cancer | sensitive | Tankyrase Inhibitor | XAV939 | Preclinical | Actionable | In a preclinical study, XAV939 inhibited growth of colorectal cancer cells harboring APC inactivating mutations in culture (PMID: 19759537). | 19759537 |
APC inact mut | colon carcinoma | sensitive | CTNNB1 Inhibitor | FH535 | Preclinical | Actionable | In a preclinical study, FH535 inhibited beta-catenin/TCF-dependent transactivation and demonstrated toxicity in colon carcinoma cells harboring an APC mutation in culture (PMID: 18347139). | 18347139 |
APC inact mut | colorectal cancer | sensitive | CTNNB1 Inhibitor | PKF118-310 | Preclinical | Actionable | In a preclinical study, PKF118-310 inhibited proliferation of colorectal cancer cell line harboring an APC inactivating mutation in culture (PMID: 14749129). | 14749129 |
APC inact mut | colorectal cancer | sensitive | CTNNB1 Inhibitor | CCT036477 | Preclinical | Actionable | In a preclinical study, CCT036477 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC inactivating mutations in culture (PMID: 20610623). | 20610623 |
APC inact mut | colorectal cancer | sensitive | CTNNB1 Inhibitor | CCT070535 | Preclinical | Actionable | In a preclinical study, CCT070535 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC inactivating mutations in culture (PMID: 20610623). | 20610623 |
APC inact mut | colorectal cancer | sensitive | CTNNB1 Inhibitor | CCT031374 | Preclinical | Actionable | In a preclinical study, CCT031374 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC inactivating mutations in culture (PMID: 20610623). | 20610623 |
APC inact mut | colon cancer | sensitive | CTNNB1 Inhibitor | iCRT-3 | Preclinical | Actionable | In a preclinical study, iCRT-3 induced cell-cycle arrest and inhibited proliferation of colon cancer cells harboring APC inactivating mutations in culture (PMID: 21393571). | 21393571 |
APC inact mut | colorectal cancer | sensitive | CTNNB1 Inhibitor | NC043 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, NC043 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC truncation mutations in culture and in cell line xenograft models (PMID: 21321609). | 21321609 |
APC inact mut | colon cancer | sensitive | Tankyrase Inhibitor | JW55 | Preclinical | Actionable | In a preclinical study, JW55 inhibited proliferation of colorectal cancer cells with an APC truncation mutation in culture and decreased tumor development in a mouse model expressing a conditional APC truncation mutation (PMID: 22440753). | 22440753 |
APC inact mut | colorectal cancer | sensitive | CTNNB1 Inhibitor | Pyrvinium | Preclinical | Actionable | In a preclinical study, Pyrvinium inhibited Wnt signaling and decreased viability of colon cancer cells harboring APC mutations in culture (PMID: 20890287). | 20890287 |
APC inact mut | colon cancer | sensitive | CTNNB1 Inhibitor | iCRT-5 | Preclinical | Actionable | In a preclinical study, iCRT-5 induced cell-cycle arrest and inhibited proliferation of colon cancer cells harboring APC inactivating mutations in culture (PMID: 21393571). | 21393571 |
APC inact mut | colon cancer | sensitive | CTNNB1 Inhibitor | iCRT-14 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, iCRT-14 induced cell-cycle arrest and inhibited proliferation of colon cancer cells harboring APC inactivating mutations in culture and decreased initial tumor growth in APC-mutant colon cancer cell line xenograft models (PMID: 21393571). | 21393571 |
APC inact mut | colon cancer | sensitive | Tankyrase Inhibitor | G007-LK | Preclinical - Cell line xenograft | Actionable | In a preclinical study, G007-LK inhibited growth of APC-mutant colorectal cancer cell lines in culture and in xenograft models (PMID: 23539443). | 23539443 |
APC inact mut | colorectal cancer | sensitive | CTNNB1 Inhibitor | Niclosamide | Preclinical | Actionable | In a preclinical study, Niclosamide inhibited proliferation of colorectal cancer cells harboring APC mutations in culture (PMID: 21531761). | 21531761 |
APC inact mut | colorectal cancer | sensitive | TASIN-1 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TASIN-1 efficiently inhibited survival of colorectal cancer cell lines harboring APC truncation mutations in culture and in cell line xenograft models (PMID: 27798265). | 27798265 | |
APC inact mut | prostate cancer | decreased response | Abiraterone | Clinical Study | Actionable | In a clinical study, metastatic castrate-resistant prostate cancer patients harboring a Wnt pathway activating alteration demonstrated shorter median overall survival (23.6 mo vs 27.7 mo) and median time to PSA progression (6.5 mo vs 9.6 mo) following Zytiga (abiraterone) or Xtandi (enzalutamide) treatment compared to patients without Wnt pathway alterations, and APC or RNF43 inactivating mutations were independently associated with increased hazard of PSA progression (aHR 1.83; p=0.004) (PMID: 31176623). | 31176623 | |
APC inact mut | prostate cancer | decreased response | Enzalutamide | Clinical Study | Actionable | In a clinical study, metastatic castrate-resistant prostate cancer patients harboring a Wnt pathway activating alteration demonstrated shorter median overall survival (23.6 mo vs 27.7 mo) and median time to PSA progression (6.5 mo vs 9.6 mo) following Zytiga (abiraterone) or Xtandi (enzalutamide) treatment compared to patients without Wnt pathway alterations, and APC or RNF43 inactivating mutations were independently associated with increased hazard of PSA progression (aHR 1.83; p=0.004) (PMID: 31176623). | 31176623 | |
APC inact mut | desmoid tumor | predicted - sensitive | BMS-906024 | Case Reports/Case Series | Actionable | In a clinical case study, BMS-906024 treatment resulted in a partial response that lasted for at least 2.6 years in a patient with a desmoid tumor harboring an inactivating APC mutation (PMID: 34590610). | 34590610 | |
APC inact mut | desmoid tumor | predicted - sensitive | Nirogacestat | Case Reports/Case Series | Actionable | In a clinical case study, Ogsiveo (nirogacestat) resulted in stable disease lasting 9 months in a patient with a patient with a desmoid tumor harboring an inactivating APC mutation (PMID: 32762028). | 32762028 |