biostudies-literatureLiu YBeijing Municipal Health CommissionNational Natural Science Foundation of ChinaCapital Funds for Health Improvement and Researche70124https://www.ebi.ac.uk/biostudies/studies/S-EPMC11570871biostudies-literatureUnknown30(11)<h4>Aims</h4>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-2021, a third-generation oncolytic adenovirus, combined with the PARP inhibitor olaparib in GBM.<h4>Methods</h4>TS-2021's impact on p66shc-induced apoptosis, DNA damage response, and poly (ADP-ribose) polymerase (PARP) activation was evaluated in GBM cells. The synergistic effect of TS-2021 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.<h4>Results</h4>TS-2021 triggered p66shc-induced apoptosis, DNA damage response, and PARP activation. The combination of TS-CNS neuroscience & therapeuticsOlaparib Enhances the Efficacy of Third-Generation Oncolytic Adenoviruses Against Glioblastoma by Modulating DNA Damage Response and p66shc-Induced Apoptosis.PMC1157087111000023T000002044300-311000023T000002044300‐3CFH,2024-1-107152373129Liu YWang PZhang JFang SLiu FfalseOlaparib Enhances the Efficacy of Third-Generation Oncolytic Adenoviruses Against Glioblastoma by Modulating DNA Damage Response and p66shc-Induced Apoptosis.<h4>Aims</h4>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-2021, a third-generation oncolytic adenovirus, combined with the PARP inhibitor olaparib in GBM.<h4>Methods</h4>TS-2021's impact on p66shc-induced apoptosis, DNA damage response, and poly (ADP-ribose) polymerase (PARP) activation was evaluated in GBM cells. The synergistic effect of TS-2021 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.<h4>Results</h4>TS-2021 triggered p66shc-induced apoptosis, DNA damage response, and PARP activation. The combination of TS-2024-01-01T00:00:00Z2024 Nov2026-07-16T23:50:07.475Z2025-04-07T10:10:06.338ZS-EPMC115708713955245010.1111/cns.70124