AI Article Synopsis
- ATM is crucial for managing DNA damage and stress responses, influencing processes like DNA repair, apoptosis, and cell proliferation.
- Germline variants in the ATM gene are linked to increased cancer risks, especially for breast and pancreatic cancers.
- Current research is exploring synthetic lethality by inhibiting alternative DNA repair pathways in cancers deficient in ATM, with ongoing clinical trials assessing DNA damage response inhibitors.
Article 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 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 gene, function of ATM kinase, clinical significance of germline pathogenic variants in patients with hereditary cancers, and ongoing efforts to target ATM for the benefit of cancer patients.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8745051 | PMC |
| http://dx.doi.org/10.3390/ijms23010523 | DOI Listing |
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