{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:30:24Z","timestamp":1787243424773,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>WEE1 plays an important role in the regulation of cell cycle G2\/M checkpoints and DNA damage response (DDR). Inhibition of WEE1 can increase the instability of the genome and have anti\u2013tumor effects in some solid tumors. However, it has certain limitations for multiple cancer cells from different lineages. Therefore, we consider the use of synthetic lethal interactions to enhance the therapeutic effect. Our experiments proved that WEE1 inhibitor (WEE1i) can activate the ataxia telangiectasia and RAD3\u2010related (ATR) pathway and that blockage of ATR dramatically sensitized the WEE1i\u2010induced cell death. The tumor\u2010selective synthetic lethality between bioavailable WEE1 and ATR inhibitors led to tumor remission in\u00a0vivo. Mechanistically, the combination promoted the accumulation of cytosolic double\u2010strand DNA, which subsequently activated the stimulator of the interferon gene (STING) pathway and induced the production of type\u00a0I interferon and CD8+ T cells, thereby inducing anti\u2013tumor immunity. Furthermore, our study found that immune checkpoint programmed death\u2010ligand 1 is upregulated by the combination therapy, and blocking PD\u2010L1 further enhances the effect of the combination therapy. In summary, as an immunomodulator, the combination of WEE1i with ATR inhibitor (ATRi) and immune checkpoint blockers provides a potential new approach for cancer treatment.<\/jats:p>","DOI":"10.1111\/cas.15108","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T02:00:56Z","timestamp":1628733656000},"page":"4444-4456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["WEE1 inhibitor and ataxia telangiectasia and RAD3\u2010related inhibitor trigger stimulator of interferon gene\u2010dependent immune response and enhance tumor treatment efficacy through programmed death\u2010ligand 1 blockade"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6793-9918","authenticated-orcid":false,"given":"Xue","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Tongji Hospital Tongji Medical College Huazhong University 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