Abstract Aim Mebendazole (MBZ), a benzimidazole anthelmintic with established clinical use, has emerged as a repurposing candidate for primary brain tumours due to its multimodal anticancer actions and central nervous system penetrance. This systematic review synthesizes preclinical and clinical evidence evaluating MBZ's efficacy, mechanisms of action and translational relevance. Methods This systematic review was conducted in accordance with the Joanna Briggs Institute (JBI) methodology. Systematic searches were performed in PubMed, EMBASE, SCOPUS and Web of Science using predefined eligibility criteria. A total of 22 studies were included (17 preclinical and five clinical/population). Results Preclinical work across glioblastoma, diffuse midline glioma, medulloblastoma and meningioma demonstrates consistent tumour growth suppression and survival extension via microtubule depolymerization, kinase inhibition, angiogenesis blockade, Hedgehog pathway interference, apoptosis/pyroptosis induction and impairment of DNA repair. MBZ also potentiates standard therapies, enhancing the effects of alkylators, radiotherapy and autophagy inhibitors. Efficacy was influenced by formulation, with polymorph C demonstrating superior brain penetration and tolerability. Additional delivery strategies, including efflux inhibition, intranasal microemulsions and nanosuspensions, further improved exposure. Clinically, MBZ was generally tolerable at high oral doses in early‐phase studies, but evidence of efficacy remained modest, inconsistent and inconclusive. Conclusion MBZ shows broad preclinical anticancer activity and acceptable tolerability in early human studies, but current clinical evidence does not demonstrate meaningful efficacy in brain tumour patients. Further well‐designed comparative trials with clear formulation reporting and integrated pharmacokinetic and biomarker analyses are needed.
Blum et al. (2026) studied this question.