Molecular Profile Detail

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Profile Name ATM loss
Gene Variant Detail

ATM loss (loss of function)

Relevant Treatment Approaches Olaparib

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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
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