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Molecular Profile Detail

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Profile Name CTNNB1 H36Y
Gene Variant Detail

CTNNB1 H36Y (gain of function - predicted)

Relevant Treatment Approaches CTNNB1 Inhibitor PDPK1 Inhibitor Tankyrase Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
CTNNB1 mutant colorectal cancer sensitive BC21 Preclinical Actionable In a preclinical study, BC21 inhibited growth and viability of a colorectal cancer cell line with a CTNNB1 mutation and increased beta-catenin expression in culture (PMID: 22224445). 22224445
CTNNB1 mutant hepatocellular carcinoma sensitive PMED-1 Preclinical Actionable In a preclinical study, PMED-1 decreased Wnt expression and decreased proliferation of hepatocellular carcinoma cells with Ctnnb1 mutations (PMID: 24819961). 24819961
CTNNB1 act mut desmoid tumor sensitive Imatinib Clinical Study - Cohort Actionable In a retrospective analysis, patients with desmoid fibromatosis harboring CTNNB1 activating exon 3 mutations demonstrated a greater progression arrest rate at 6 months compared to patients with CTNNB1 wild-type tumor when treated with Gleevec (imatinib) (PMID: 26861905). 26861905
CTNNB1 mutant endometrial cancer predicted - sensitive Temsirolimus Phase II Actionable In a retrospective study of a Phase II trial, Torisel (temsirolimus) treatment resulted in an increased progression-free survival (HR 0.46) but not response rate (response difference 0.00) in advanced endometrial cancer patients harboring CTNNB1 mutations (PMID: 27016228). 27016228
CTNNB1 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...
CTNNB1 act mut hepatocellular carcinoma decreased response unspecified PD-1 antibody Clinical Study - Cohort Actionable n a clinical study, treatment with immune checkpoint antibodies, including anti-PD-1, anti-PD-L1, or anti-CTLA-4 monotherapy or combinations of anti-PD-1 with anti-CTLA-4, anti-LAG3, or anti-KIR, was less effective in hepatocellular carcinoma patients with Wnt pathway mutations in CTNNB1 or AXIN1 compared to patients without Wnt pathway mutations, with 0% (0/10) vs. 53% (9/17) achieving disease control, respectively, and shorter progression-free survival (2.0 mo vs. 7.4 mo) (PMID: 30373752; NCT01775072). 30373752
CTNNB1 act mut hepatocellular carcinoma decreased response unspecified PD-L1 antibody Clinical Study - Cohort Actionable In a clinical study, treatment with immune checkpoint antibodies, including anti-PD-1, anti-PD-L1, or anti-CTLA-4 monotherapy or combinations of anti-PD-1 with anti-CTLA-4, anti-LAG3, or anti-KIR, was less effective in hepatocellular carcinoma patients with Wnt pathway mutations in CTNNB1 or AXIN1 compared to patients without Wnt pathway mutations, with 0% (0/10) vs. 53% (9/17) achieving disease control, respectively, and shorter progression-free survival (2.0 mo vs. 7.4 mo) (PMID: 30373752; NCT01775072). 30373752
CTNNB1 act mut hepatocellular carcinoma decreased response unspecified CTLA4 antibody Clinical Study - Cohort Actionable In a clinical study, treatment with immune checkpoint antibodies, including anti-PD-1, anti-PD-L1, or anti-CTLA-4 monotherapy or combinations of anti-PD-1 with anti-CTLA-4, anti-LAG3, or anti-KIR, was less effective in hepatocellular carcinoma patients with Wnt pathway mutations in CTNNB1 or AXIN1 compared to patients without Wnt pathway mutations, with 0% (0/10) vs. 53% (9/17) achieving disease control, respectively, and shorter progression-free survival (2.0 mo vs. 7.4 mo) (PMID: 30373752; NCT01775072). 30373752
CTNNB1 act mut hepatocellular carcinoma decreased response unspecified CTLA4 antibody + unspecified PD-1 antibody Clinical Study - Cohort Actionable In a clinical study, treatment with immune checkpoint antibodies, including anti-PD-1, anti-PD-L1, or anti-CTLA-4 monotherapy or combinations of anti-PD-1 with anti-CTLA-4, anti-LAG3, or anti-KIR, was less effective in hepatocellular carcinoma patients with Wnt pathway mutations in CTNNB1 or AXIN1 compared to patients without Wnt pathway mutations, with 0% (0/10) vs. 53% (9/17) achieving disease control, respectively, and shorter progression-free survival (2.0 mo vs. 7.4 mo) (PMID: 30373752; NCT01775072). 30373752
CTNNB1 mutant desmoid tumor not applicable N/A Guideline Diagnostic CTNNB1 mutations aid the diagnosis of desmoid tumor (NCCN.org). detail...
CTNNB1 mutant endometrial cancer predicted - sensitive Cabozantinib Case Reports/Case Series Actionable In a Phase II (NCI9322/PHL86) trial, Cometriq (Cabometyx, cabozantinib) treatment resulted in a response rate of 40% (4/10) and a 12-week progression-free survival rate of 70% (7/10) in patients with endometrial cancer harboring CTNNB1 mutations, with a median PFS of 7.6 months (PMID: 31992589; NCT01935934). 31992589
CTNNB1 act mut lung non-small cell carcinoma predicted - resistant Osimertinib Case Reports/Case Series Actionable In a retrospective analysis, activating CTNNB1 mutations including S37F/C (n=5), D32V (n=1), G34V (n=1), and T41I (n=1) were identified in 8 of 100 patients with non-small cell lung cancer at treatment discontinuation of Tagrisso (osimertinib) (PMID: 31839416). 31839416
CTNNB1 act mut Advanced Solid Tumor predicted - sensitive CC-91516 Preclinical - Patient cell culture Actionable In a preclinical study, CC-91516 treatment induced apoptosis and inhibited viability of cancer cells harboring CTNNB1 activating mutations, and inhibited ex vivo colony formation from patient-derived xenograft (PDX) models in culture (Cancer Res 2022;82(12_Suppl):Abstract nr 1180). detail...
CTNNB1 mutant hepatocellular carcinoma predicted - sensitive WNTinib Preclinical - Cell culture Actionable In a preclinical study, WNTinib inhibited Ezh2 phosphorylation and viability in a hepatocellular carcinoma cell line harboring a deletion of CTNNB1 exons in culture (PMID: 37537299). 37537299
CTNNB1 act mut hepatocellular carcinoma sensitive WNTinib Preclinical Actionable In a preclinical study, WNTinib increased survival in a mouse model of CTNNB1-driven hepatocellular carcinoma (PMID: 37537299). 37537299