biostudies-literatureIvanova AKeenan Chair in SurgeryGratitude 10Ontario Graduate ScholarshipBrainchildOxford University PressCalum Macbeth Fundthe Early Research Award from the Province of OntarioMeagan’s WalkCanadian Institutes of Health Researche186703https://www.ebi.ac.uk/biostudies/studies/S-EPMC12487684biostudies-literatureUnknown10(17)More than a third of patients with glioblastoma experience tumor progression during adjuvant therapy. In this study, we performed a high-throughput drug repurposing screen of FDA-approved agents capable of crossing the blood-brain barrier in order to find agents to counteract acquired or inherent glioma cell resistance to temozolomide-associated cytotoxicity. We identified the cholesterol processing inhibitor, lomitapide, as a potential chemosensitizer in glioblastoma. In vitro treatment of temozolomide-resistant glioblastoma cells with lomitapide resulted in decreased intracellular ubiquinone levels and sensitized cells to temozolomide-induced ferroptosis. Concomitant treatment with lomitapide and temozolomide (TMZ) prolonged survival and delayed tumor recurrence in a mouse glioblastoma mJCI insightLomitapide enhances cytotoxic effects of temozolomide in chemotherapy-resistant glioblastoma.PMC12487684VPiXKeenan Chair in SurgeryroyaltiesBrainchildCalum Macbeth FundSynaptiveOGSthe Early Research Award from the Province of OntarioMeagan’s WalkCIHR-OG-341329philanthropic fundsIvanova AWu MDas SFlick RWilson TMGhannad-Zadeh KTse EfalseLomitapide enhances cytotoxic effects of temozolomide in chemotherapy-resistant glioblastoma.More than a third of patients with glioblastoma experience tumor progression during adjuvant therapy. In this study, we performed a high-throughput drug repurposing screen of FDA-approved agents capable of crossing the blood-brain barrier in order to find agents to counteract acquired or inherent glioma cell resistance to temozolomide-associated cytotoxicity. We identified the cholesterol processing inhibitor, lomitapide, as a potential chemosensitizer in glioblastoma. In vitro treatment of temozolomide-resistant glioblastoma cells with lomitapide resulted in decreased intracellular ubiquinone levels and sensitized cells to temozolomide-induced ferroptosis. Concomitant treatment with lomitapide and temozolomide (TMZ) prolonged survival and delayed tumor recurrence in a mouse glioblastoma m2025-01-01T00:00:00Z2025 Sep2026-06-04T01:23:42.21Z2026-05-03T03:13:57.749ZS-EPMC124876844092332010.1172/jci.insight.186703