ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors

Ataxia-telangiectasia mutated (ATM) functions as a key initiator and coordinator of DNA damage and cellular stress responses. ATM signaling pathways contain many downstream targets that regulate multiple important cellular processes, including DNA damage repair, apoptosis, cell cycle arrest, oxidative sensing, and proliferation. Over the past few decades, associations between germline ATM pathogenic variants and cancer risk have been reported, particularly for breast and pancreatic cancers. In addition, given that ATM plays a critical role in repairing double-strand breaks, inhibiting other DNA repair pathways could be a synthetic lethal approach. Based on this rationale, several DNA damage response inhibitors are currently being tested in ATM-deficient cancers. In this review, we discuss the current knowledge related to the structure of the ATM gene, function of ATM kinase, clinical significance of ATM germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.

Automated summary

ATM serves as a crucial regulator of DNA damage and cellular stress responses, influencing various cellular processes such as DNA repair, apoptosis, and cell cycle regulation. Germline ATM pathogenic variants have been linked to an increased risk of cancers, particularly breast and pancreatic cancers. Inhibiting alternative DNA repair pathways may be a potential strategy for targeting ATM-deficient cancers.