Fenbendazole As a Radiosensitizer in Stage 4 Cancer
Fenbendazole is a widely used antiparasitic drug. It has a long track record of safety for use as an animal anthelmintic and gives substantial egg count reductions against the parasites Ascaris, hookworm and Trichuris in humans. It has also been shown to have potent anti-cancer activity in laboratory experiments. It is a member of the benzimidazole family of anti-cancer agents and has been shown to suppress tumor growth in preclinical models.
This study explores the hypothesis that fenbendazole acts as a radiosensitizer by inhibiting microtubule polymerization in hypoxic cancer cells. In this investigation, we compared the radiation sensitivity of EMT6 cells treated with or without fenbendazole in vitro under aerobic and hypoxic conditions. The dose-response curves for both conditions were determined using a colony formation assay. Results from these experiments indicated that fenbendazole did not alter the radiation response of hypoxic EMT6 cells. However, a 2-h treatment with 10 mM fenbendazole significantly reduced the survival of aerobic EMT6 cells treated with docetaxel under hypoxic conditions. When these toxicity data were normalized to account for the toxicity of fenbendazole alone, the addition of fenbendazole increased the overall cytotoxic effect of docetaxel. This increase in toxicity was confirmed by isobologram analysis.
To examine whether fenbendazole could act as a radiosensitizer in vivo, we administered three daily i.p. injections of fenbendazole to tumor-bearing BALB/c mice and then irradiated these mice with 10 Gy of x-rays. This experiment and a second one (data not shown) showed that fenbendazole did no alter tumor growth in unirradiated mice or slow the rate of tumor growth to four-fold its initial volume after irradiation. fenbendazole stage 4 cancer