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Boron neutron capture therapy (BNCT) has emerged as a promising modality that delivers selective cytotoxicity to recurrent GBM, yet its efficacy is constrained by tumor-intrinsic DNA repair mechanisms. Targeting DNA repair pathways may therefore represent a rational strategy to potentiate BNCT and improve outcomes in TMZ-resistant GBM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated whether combining BPA-mediated BNCT with the PARP inhibitor olaparib enhances efficacy in temozolomide (TMZ)-resistant U-87 TR and parental U-87 MG GBM cells. Clonogenic assays were used to quantify cytotoxicity, while mechanistic studies evaluated DNA damage, cell cycle arrest, and apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Olaparib significantly sensitized GBM cells to BNCT, reducing survival to 40.7\u2009\u00b1\u20098.1% in U-87 MG and 24.2\u2009\u00b1\u20098.3% in U-87 TR cells, with radiation enhancement ratios of 1.53 and 1.95, respectively. In U-87 TR cells, the combination treatment induced persistent \u03b3H2AX foci, sustained G\n                      <jats:sub>2<\/jats:sub>\n                      \/M arrest, and suppressed BNCT-driven upregulation of BRCA1 and RAD51, indicating impaired HR repair. Apoptosis was markedly increased in both cell lines, proceeding through PUMA\u2013BAX activation in U-87 MG and via PUMA-independent pathways in U-87 TR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PARP inhibition (Olaparib) enhances BNCT-induced DNA damage, disrupts HR repair, and induces apoptosis through distinct mechanisms in sensitive and resistant GBM cells. These findings provide mechanistic evidence for BNCT\u2013PARP inhibitor combinations as a strategy to overcome therapeutic resistance and merit further translational and clinical investigation in TMZ-resistant GBM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11604-025-01929-9","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T04:32:12Z","timestamp":1766550732000},"page":"949-962","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PARP Inhibition potentiates boron neutron capture therapy in chemoresistant glioblastoma via DNA repair disruption"],"prefix":"10.1007","volume":"44","author":[{"given":"Ting-Yu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zih-Yin","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Jung","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Shun","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fong-In","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6022-0107","authenticated-orcid":false,"given":"Yung-Jen","family":"Chuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"1929_CR1","doi-asserted-by":"publisher","first-page":"574012","DOI":"10.3389\/fonc.2020.574012","volume":"10","author":"B Oronsky","year":"2020","unstructured":"Oronsky B, et al. 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