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Profile Name | ATM mutant |
Gene Variant Detail | |
Relevant Treatment Approaches |
Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|---|
ATM mutant | prostate cancer | sensitive | Olaparib | Phase II | Actionable | In a Phase II clinical trial, 80% (4/5) of metastatic castration-resistant prostate cancer patients with ATM truncation mutations demonstrated response to Lynparza (olaparib) treatment (Cancer Res August 1, 2015 75:CT322). | detail... | |
ATM mutant | mantle cell lymphoma | predicted - sensitive | Ibrutinib + Venetoclax | Phase II | Actionable | In a Phase II trial (AIM), distinct molecular profiles were identified in mantle cell lymphoma patients responded to Imbruvica (ibrutinib) and Venclexta (venetoclax) combination therapy compared to those did not respond, with all patients harboring mutations in NSD2 (n=4), UBR5 (n=3), KMT2D (n=3), and 12 of 13 patients harboring mutations in ATM responded to the therapy, while SMARCA4 (n=4), CCND1 (n=2), and NOTCH1 (n=3) alterations were exclusively observed in nonresponders (PMID: 30455436; NCT02471391). | 30455436 | |
ATM mutant | prostate cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing prostate cancer (NCCN.org). | detail... | |
ATM mutant | breast cancer | no benefit | Olaparib | Case Reports/Case Series | Actionable | In a Phase II trial (TBCRC 048), Lynparza (olaparib) treatment did not result in an objective response in 4 patients with metastatic breast cancer harboring only germline mutations in ATM (PMID: 33119476; NCT03344965). | 33119476 | |
ATM mutant | Advanced Solid Tumor | conflicting | Olaparib | Phase II | Actionable | In a Phase II trial (TAPUR), Lynparza (olaparib) treatment resulted in an objective response rate of 8% and a disease control rate of 25% (9/36, 1 complete response, 2 partial responses, 6 stable disease at 16+ weeks) in patients with advanced solid tumors harboring ATM mutations (Cancer Res 2022;82(12_Suppl):Abstract nr CT110; NCT02693535). | detail... | |
ATM mutant | Advanced Solid Tumor | conflicting | Olaparib | Phase II | Actionable | In a Phase II trial, Lynparza (olaparib) treatment did not demonstrate clinical activity in patients with advanced solid tumors harboring ATM (n=13) or CHEK2 (n=14) mutations (Ann Oncol (2023) 34 (suppl_2): S242; NCT03967938). | detail... | |
ATM mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing breast cancer (NCCN.org). | detail... | |
ATM mutant | lung non-small cell carcinoma | predicted - sensitive | M1774 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, M1774 inhibited tumor growth in a cell line xenograft model of non-small cell lung cancer harboring an ATM mutation (PMID: 38407317). | 38407317 | |
ATM mutant | ovarian cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing ovarian cancer (NCCN.org). | detail... | |
ATM mutant | pancreatic cancer | not applicable | N/A | Guideline | Risk Factor | Germline ATM mutations are associated with increased risk of developing pancreatic cancer (NCCN.org). | detail... | |
ATM mutant | chronic lymphocytic leukemia/small lymphocytic lymphoma | not applicable | N/A | Guideline | Prognostic | ATM mutations are associated with shorter time to first treatment, progression-free survival, time to next treatment, and overall survival with chemoimmunotherapy compared to wild-type ATM in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (NCCN.org). | detail... |