{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T03:51:52Z","timestamp":1777089112577,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52373129"],"award-info":[{"award-number":["52373129"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005088","name":"Beijing Municipal Health Commission","doi-asserted-by":"publisher","award":["11000023T000002044300\u20103"],"award-info":[{"award-number":["11000023T000002044300\u20103"]}],"id":[{"id":"10.13039\/501100005088","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Patients with glioblastoma multiforme (GBM) do not benefit from current cancer treatments, and their prognosis is dismal. This study aimed to investigate the potential synergistic effects of TS\u20102021, a third\u2010generation oncolytic adenovirus, combined with the PARP inhibitor olaparib in GBM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>TS\u20102021\u2019s impact on p66shc\u2010induced apoptosis, DNA damage response, and poly (ADP\u2010ribose) polymerase (PARP) activation was evaluated in GBM cells. The synergistic effect of TS\u20102021 and olaparib was examined in GBM cell lines and an immunocompetent mouse model of GBM. Mechanistic studies focused on the role of p66shc phosphorylation in the observed effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>TS\u20102021 triggered p66shc\u2010induced apoptosis, DNA damage response, and PARP activation. The combination of TS\u20102021 and olaparib synergistically increased cell apoptosis and DNA damage and reduced PARP expression compared to monotherapy. Olaparib promoted TS\u20102021 replication and release in GBM cells. Mechanistically, olaparib combined with TS\u20102021 upregulated p66shc phosphorylation, enhancing tumor cell apoptosis. In\u00a0vivo, the combination therapy inhibited tumor growth and prolonged survival, confirming the synergistic effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first to suggest that TS\u20102021 sensitizes GBM cells with wild\u2010type BRCA1\/2 to olaparib. The combination of TS\u20102021 and olaparib shows a synergistic therapeutic effect against GBM, providing a promising treatment strategy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70124","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T09:36:23Z","timestamp":1731922583000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Olaparib Enhances the Efficacy of Third\u2010Generation Oncolytic Adenoviruses Against Glioblastoma by Modulating <scp>DNA<\/scp> Damage Response and p66shc\u2010Induced Apoptosis"],"prefix":"10.1111","volume":"30","author":[{"given":"Yida","family":"Liu","sequence":"first","affiliation":[{"name":"Brain Tumor Research Center, Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery Beijing Tiantan Hospital Affiliated to Capital Medical University  Beijing China"},{"name":"Beijing Laboratory of Biomedical 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