Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme

TLDR

Glioblastoma multiforme remains highly lethal despite advances, and the FDA‑approved anti‑helminthic mebendazole, with a long safety record, shows promise in preclinical models. The authors screened benzimidazoles and identified mebendazole as the most effective agent for GBM therapy. Mebendazole killed GBM cells at sub‑micromolar concentrations, disrupted microtubules, and increased mouse survival by up to 63 %, suggesting it is a promising candidate for clinical trials.

Abstract

Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytotoxicity, with half-maximal inhibitory concentrations ranging from 0.1 to 0.3 µM. Mebendazole disrupted microtubule formation in GBM cells, and in vitro activity was correlated with reduced tubulin polymerization. Subsequently, we showed that mebendazole significantly extended mean survival up to 63% in syngeneic and xenograft orthotopic mouse glioma models. Mebendazole has been approved by the US Food and Drug Administration for parasitic infections, has a long track-record of safe human use, and was effective in our animal models with doses documented as safe in humans. Our findings indicate that mebendazole is a possible novel anti-brain tumor therapeutic that could be further tested in clinical trials.