ATM: Functions of ATM Kinase and Its Relevance to Hereditary Tumors |
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Authors: | Sayaka Ueno Tamotsu Sudo Akira Hirasawa |
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Affiliation: | 1.Section of Translational Research, Hyogo Cancer Center, 13-70 Kita-Oji-cho, Akashi-shi 673-8558, Japan;2.Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan; |
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Abstract: | 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. |
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Keywords: | hereditary tumors ATM DNA damage redox homeostasis tumor profiling precision therapy |
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