{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T06:42:31Z","timestamp":1789800151441,"version":"4.0.1"},"reference-count":144,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastric cancer remains a significant global health challenge, with regional and demographic disparities in incidence, mortality, and treatment outcomes. Despite advances in screening and early detection, prognosis remains poor for many patients, particularly those with advanced disease. Recent insights into DNA damage response pathways have uncovered critical molecular vulnerabilities in gastric tumors, including frequent TP53 mutations, ARID1A loss, ATM deficiency, and oncogene-driven replication stress, which render these cancers highly dependent on the ATR\u2013CHK1 axis for survival. This review synthesizes current clinical and preclinical evidence on ATR and CHK1 inhibitors as therapeutic strategies in gastric cancer. Emphasis is placed on synthetic lethality, immune modulation, and the potential for combination regimens with chemotherapy, radiotherapy, or immune checkpoint blockade. Mechanisms of resistance, including transcription-associated replication stress modulation and bypass signaling networks, are discussed, alongside strategies to predict and overcome therapeutic failure. The review also highlights the importance of biomarker-guided patient selection, adaptive dosing to reduce toxicity, and refined pharmacodynamic monitoring to enhance therapeutic precision. Collectively, these insights support the rational integration of ATR\u2013CHK1 inhibitors into clinical protocols for biomarker-defined gastric cancer subsets and underscore their promise<\/jats:p>","DOI":"10.3390\/ijms26167709","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:02:09Z","timestamp":1754910129000},"page":"7709","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["ATR-CHK1 Axis Inhibitors in Gastric Cancer Treatment"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8616-3825","authenticated-orcid":false,"given":"Mateusz","family":"Kciuk","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Gruszka","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-7662","authenticated-orcid":false,"given":"Marta","family":"Aleksandrowicz","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical Research and Environmental Agents, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawi\u0144skiego Street, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6864-0704","authenticated-orcid":false,"given":"Agnieszka","family":"\u015aliwi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Nucleic Acid Biochemistry, Medical University of Lodz, Pomorska 251, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2859-9839","authenticated-orcid":false,"given":"Renata","family":"Kontek","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Genetics, Faculty of Biology and Environmental Protection, University of Lodz, Banacha Street 12\/16, 90-237 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Inoue, M. (2024). 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