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Gene | ATM |
Variant | loss |
Impact List | unknown |
Protein Effect | loss of function |
Gene Variant Descriptions | ATM loss indicates loss of the ATM gene, mRNA, and protein. |
Associated Drug Resistance | |
Category Variants Paths |
ATM mutant ATM inact mut ATM loss |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
ATM loss | chronic lymphocytic leukemia | sensitive | AZD6482 | Preclinical | Actionable | In a preclinical study, AZD6482 induced cell death in ATM-deficient chronic lymphocytic leukemia cells in culture and inhibited tumor growth in xenograft models (PMID: 26563132). | 26563132 |
ATM loss | colorectal cancer | sensitive | Berzosertib | Phase I | Actionable | In a Phase I trial, Berzosertib (VX-970) treatment resulted in complete response for more than 19 months in a colorectal cancer patient harboring ATM loss (J Clin Oncol 34, 2016 (suppl; abstr 2504)). | detail... |
ATM loss | lung non-small cell carcinoma | sensitive | Ceralasertib + Cisplatin | Preclinical | Actionable | In a preclinical study, AZD6738 and Platinol (cisplatin) synergistically induced cell death in ATM-deficient non-small cell lung carcinoma cell lines in culture, and caused rapid tumor regression in xenograft models (PMID: 26517239). | 26517239 |
ATM loss | chronic lymphocytic leukemia | sensitive | Ceralasertib + Ibrutinib | Preclinical | Actionable | In a preclinical study, AZD6738 sensitized ATM-deficient chronic lymphocytic leukemia cells to Imbruvica (Ibrutinib) treatment in culture (PMID: 26563132). | 26563132 |
ATM loss | Advanced Solid Tumor | sensitive | YU238259 | Preclinical | Actionable | In a preclinical study, YU238259 demonstrated increased cytotoxicity in ATM-deficient transformed human cell lines in culture (PMID: 26116172). | 26116172 |
ATM loss | head and neck cancer | predicted - sensitive | Ceralasertib + Olaparib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of AZD6738 and Lynparza (olaparib) resulted in a synergistic effect, demonstrating cell death in head and neck cancer cells harboring ATM loss in culture (Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C60). | detail... |
ATM loss | triple-receptor negative breast cancer | predicted - sensitive | Ceralasertib + Olaparib | Phase II | Actionable | In a Phase II trial (plasmaMATCH), treatment with the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in limited efficacy in patients with advanced triple-negative breast cancer, with an objective response rate of 17.1% (12/70), but in patients with wild-type BRCA1/2 and ATM loss, resulted in a median progression-free survival of 3.4 vs 2.5 mo and response rate of 21.4 (3/14) vs 13.8% (4/29) in patients without loss of ATM (PMID: 37773077; NCT03182634). | 37773077 |
ATM loss | stomach cancer | sensitive | RP-3500 | Preclinical - Pdx | Actionable | In a preclinical study, RP-3500 resulted in complete tumor regression in a gastric cancer patient-derived xenograft (PDX) model with biallelic loss of ATM (PMID: 34911817). | 34911817 |