{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T07:50:50Z","timestamp":1768809050936,"version":"3.49.0"},"reference-count":37,"publisher":"Korean Cancer Association","issue":"1","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C301088311"],"award-info":[{"award-number":["2020R1A2C301088311"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["e-crt.org"],"crossmark-restriction":true},"short-container-title":["Cancer Res Treat"],"published-print":{"date-parts":[[2026,1,15]]},"abstract":"<jats:p>Purpose Sustained cell proliferation and cell cycle acceleration in cancer cells inherently increase DNA damage, which interferes with homeostatic replication and transcription. Ataxia telangiectasia and Rad3-related (ATR) is crucial for initiation of the DNA damage response, and ATR inhibitors, such as elimusertib, induce increased replication stress and DNA damage. We investigated the anti-tumor effects of elimusertib and its mechanism of action in relation to replication stress.Materials and Methods Anti-tumor effects were evaluated by MTT assay and colony formation assay in breast cancer cell lines &lt;i&gt;in vitro&lt;\/i&gt;, in breast cancer cell xenografts &lt;i&gt;in vivo&lt;\/i&gt;, and in patient-derived xenograft models. Cell cycle was assessed by flow cytometry and BrdU assay was used to measure replicating cells and S-phase progression. Alkaline and neutral comet assay was used to measure single and double-stranded DNA damages, respectively.Results Elimusertib delayed S-phase progression in MDA-MB-453 and MDA-MB-231 cells and induced caspase-7\u2013dependent apoptosis. Furthermore, the increase in sub-G1 population in the fluorescence-activated cell sorting analysis and Annexin V assay also confirmed apoptotic cell death. In the BrdU assay, single-stranded DNA (ssDNA) increased in sensitive cells and aberrant ssDNA induced DNA damage in S-phase and eventually caused replication catastrophe. Finally, these anti-tumor effects were proven in &lt;i&gt;in vivo&lt;\/i&gt; xenograft and patient-derived xenograft models.Conclusion Elimusertib had anti-tumor effects and induced replication catastrophe in breast cancer cells with a high replication rate. Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate.<\/jats:p>","DOI":"10.4143\/crt.2024.1105","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T02:25:11Z","timestamp":1743992711000},"page":"159-174","update-policy":"https:\/\/doi.org\/10.4143\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elimusertib, a Novel ATR Inhibitor, Induces Anti-tumor Effects through Replication Catastrophe in Breast 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