{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:26Z","timestamp":1790575046053,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Glioblastoma remains one of the most treatment-resistant cancers, and temozolomide (TMZ) resistance is a central barrier to durable clinical response. Inhibition of exportin-1 (XPO1) by selinexor has emerged as a promising strategy to overcome resistance in solid tumors; however, its ability to sensitize TMZ-resistant GBM cells and the underlying mechanisms remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated selinexor and TMZ, alone and in combination, in three GBM cell lines with distinct TMZ sensitivity profiles (LN18, resistant; U87MG, moderate; LN229, sensitive), assessing viability, apoptosis, cell cycle distribution, MMR\/survival gene expression, apoptotic protein levels, and long-term colony-forming capacity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Selinexor potently sensitized GBM cells to TMZ across all three lines, with the most clinically meaningful effects observed in the TMZ-resistant background. The combination produced synergistic growth inhibition and robust apoptotic induction that neither agent achieved independently, driven by convergent suppression of MCL1 and BIRC6, partial restoration of mismatch repair gene expression, and CHK1-mediated checkpoint activation. Combination treatment induced nuclear p53 accumulation, markedly reduced BCL-2, and increased PARP cleavage, and durably suppressed long-term proliferative capacity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings position selinexor as a mechanistically rational TMZ sensitizer in resistant GBM and support further preclinical and translational investigation of this combination strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1916260","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:45:53Z","timestamp":1790574353000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Selinexor enhances temozolomide efficacy in glioblastoma through modulation of multiple resistance-associated 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