Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature

Abstract

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called “cancer stem cells”. Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

The Benzimidazole-Based Anthelmintic Parbendazole: A Repurposed Drug Candidate That Synergizes with Gemcitabine in Pancreatic Cancer

“…Conversely, the effects of the four benzimidazoles on PC cell viability did not appear to correlate with the lipophilicity of the anthelmintic drugs. Despite the different activities of the compounds, all of these drugs affected PC viability with IC 50 values in the range achieved by standard therapeutic dosages [17,[25][26][27][28].…”

“…19) µM in Capan-2 ( Figure 1B,C). These IC 50 values were all in the range or even lower than the therapeutic plasma concentrations reached after administration of standard dosages [17,[25][26][27][28]. Notably, parbendazole showed the lowest IC 50 values as compared to other benzimidazoles tested in both cell lines ( Figure 1C), suggesting that the specific substituent at the C5 might be relevant for anti-proliferative activities.…”

A systematic review of ongoing clinical trials in optic pathway gliomas

“…Other potential targets of mebendazole include the Hh signalling pathway, and angiogenesis through VEGF inhibition [ 47 ]. Repurposing of mebendazole has been suggested in various tumours and it has been previously trialled in preclinical models of glioblastoma with some success [ 48 – 50 ]. Entinostat Entinostat is a synthetic benzamide HDAC type 1 and III inhibitor.…”

Repurposing of Drug Candidates for Treatment of Skin Cancer

“…Mebendazole is a drug employed to helminths infestation ( 70 ), which has also been proposed for drug repurposing in skin cancer ( 71 ). A pioneering study exposed that mebendazole produced apoptosis in melanoma cells ( 30 ).…”