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Profile Name APC D1486fs
Gene Variant Detail

APC D1486fs (loss of function - predicted)

Relevant Treatment Approaches CTNNB1 Inhibitor Tankyrase Inhibitor

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Molecular Profile Indication/Tumor Type Response Type 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Niclosamide Preclinical Actionable In a preclinical study, Niclosamide inhibited proliferation of colorectal cancer cells harboring APC mutations in culture (PMID: 21531761). 21531761
APC mutant colorectal cancer sensitive JW74 Preclinical Actionable In a preclinical study, JW74 reduced tumor formation and growth in a mouse model of colorectal cancer harboring an APC mutation (PMID: 21199802). 21199802
APC mutant colorectal cancer no benefit G-631 Preclinical - Cell line xenograft Actionable In a preclinical study, G-631 inhibited Wnt pathway signaling in colorectal cancer cell line xenograft models harboring an APC mutation, but demonstrated little anti-tumor activity and led to intestinal toxicity (PMID: 26692561). 26692561
APC mutant colorectal cancer predicted - sensitive K-756 Preclinical Actionable In a preclinical study, K-756 inhibited Wnt signaling and reduced growth of 2/3 tested APC-mutant colorectal cancer cell lines in culture (PMID: 27196752). 27196752
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 mutant medulloblastoma not applicable N/A Guideline Prognostic WNT-driven medulloblastomas, characterized by CTNNB1 or APC mutations, are associated with favorable prognosis (NCCN.org). detail...
APC mutant colon adenoma predicted - sensitive TetMYB Preclinical Actionable In a preclinical study, TetMYB treatment resulted in improved median survival compared to control (356 vs 183 days) in APC-driven mouse models of colon adenoma (Gastroenterology, Volume 154, Issue 6, Supplement 1, May 2018, Pages S-1269). detail...
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 mutant small intestine adenocarcinoma not applicable N/A Guideline Risk Factor Familial adenomatous polyposis results from germline mutations in the APC gene, and is associated with increased risk of developing small bowel adenocarcinoma (NCCN.org). detail...
APC mutant desmoid tumor not applicable N/A Guideline Diagnostic APC mutations aid the diagnosis of desmoid tumor (NCCN.org). detail...
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
APC mutant desmoid tumor predicted - sensitive Nirogacestat Phase III Actionable In a Phase III trial (DeFi), Ogsiveo (nirogacestat) treatment resulted in improved progression-free survival (HR=0.21, p=0.016) and improved objective response rate (38% (5/13) vs. 13% (2/16)) compared to treatment with placebo in patients with desmoid tumors harboring mutations in APC (J Clin Oncol 42, 2024 (suppl 16; abstr 11558); NCT03785964). detail...