{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:04:55Z","timestamp":1789563895466,"version":"build-2803163510"},"reference-count":121,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GB) is the most aggressive primary malignant brain tumor in adults and remains associated with poor survival despite surgical resection followed by radiotherapy and temozolomide (TMZ) chemotherapy. Intrinsic and acquired resistance to TMZ, including MGMT\u2010dependent DNA repair and activation of pro\u2010survival pathways, could decrease treatment efficacy. Drug repurposing offers an attractive strategy to identify agents that may enhance TMZ activity because these drugs already have known pharmacokinetic and safety profiles. This narrative review summarizes the available evidence on repurposed drugs investigated as potential modulators of TMZ response in GB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Findings<\/jats:title>\n                    <jats:p>A range of repurposed agents, including chloroquine, valproic acid, levetiracetam, metformin, aspirin, amlodipine, atorvastatin, chlorpromazine, melatonin, disulfiram, bortezomib, and verteporfin, have been evaluated in GB models and selected clinical studies. Reported mechanisms include modulation of MGMT expression, autophagy, oxidative stress, apoptosis, DNA\u2010damage responses, cancer stem\u2010cell properties, and signaling pathways such as PI3K\/AKT\/mTOR, AMPK, EGFR, STAT3, ERK1\/2, and NF\u2010\u03baB. Several agents have enhanced TMZ\u2010associated cytotoxicity in cell culture and animal models. However, clinical evidence remains limited, and the results are inconsistent for some drugs. Blood\u2013brain barrier penetration, achievable intratumoral drug exposure, toxicity, treatment scheduling, and molecular heterogeneity of GB remain major translational challenges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Repurposed drugs may provide useful candidates for improving TMZ\u2010based therapy in GB. However, most evidence remains preclinical, and further studies are needed to clarify blood\u2013brain barrier penetration, optimal dosing, toxicity, predictive biomarkers, and clinical efficacy. Well\u2010designed prospective clinical trials are required before these combinations can be incorporated into routine GB treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70643","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T04:30:59Z","timestamp":1785990659000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Harnessing Repurposed Drugs to Enhance Temozolomide Efficacy in Glioblastoma"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9411-2846","authenticated-orcid":false,"given":"Ali","family":"Nakhaei","sequence":"first","affiliation":[{"name":"Student Research Committee, MMS.C Islamic Azad University  Mashhad Iran"},{"name":"Department of Basic Sciences, Faculty of Medicine, Mashhad Medical Sciences Islamic Azad University  Mashhad Iran"},{"name":"Bahman Educational and Medical Charity Hospital  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Taghavi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9989-9818","authenticated-orcid":false,"given":"Amir R.","family":"Afshari","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Faculty of Medicine, Mashhad Medical Sciences Islamic Azad University  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzaneh","family":"Davoudi","sequence":"additional","affiliation":[{"name":"Department of Biology, School of Computer, Mathematical, and Natural Sciences Morgan State University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaheh","family":"Gheybi","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1259-4593","authenticated-orcid":false,"given":"Mohammad","family":"Jalili\u2010Nik","sequence":"additional","affiliation":[{"name":"Pharmacological Research Center of Medicinal Plants, Basic Science Research Institute Mashhad University of Medical Sciences  Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_26_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330"},{"key":"e_1_2_26_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043331"},{"key":"e_1_2_26_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.92"},{"key":"e_1_2_26_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.168"},{"key":"e_1_2_26_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.02.012"},{"key":"e_1_2_26_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-014-1686-9"},{"issue":"1","key":"e_1_2_26_8_1","article-title":"Valproic Acid Downregulates the Expression of MGMT and Sensitizes Temozolomide\u2010Resistant Glioma Cells","volume":"2012","author":"Ryu C. 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