Recently, several websites and blogs have reported that cancer patients have experienced remission after self-administering fenbendazole, a benzimidazole antihelmintic drug. Although it is not clear why a single patient may experience such an effect, the claim has triggered widespread interest in the possibility that this drug could be effective against cancer. However, based on the currently available evidence, the claim is highly misleading.
The drug fenbendazole targets parasites by interfering with the formation of microtubules, a protein scaffolding that establishes cell shape and structure and that transports cargo within cells. Unlike textbook depictions of cells, which often look like amorphous bags of cellular components floating in a liquid, a cell actually achieves its shape and function through this dynamic protein scaffold.
Microtubules are assembled and disassembled in response to various cellular stimuli, such as changing shape to pass through narrow spaces, or when the cell is moving cargo between locations. Microtubules are also a key component of the mitotic spindle that controls cell division. In cancer cells, the cytoskeleton is often destabilized and misregulated.
In vitro, fenbendazole has a high IC50 value in cancer cells compared with normal cells, and the drug is toxic to cancer cell lines when used at relatively low concentrations. In vivo, the drug has been found to have both cytotoxic and immunomodulatory effects in mice. It has also been shown to inhibit growth of tumors in mouse models.
Based on the overlapping mechanisms of action of fenbendazole with hypoxia-selective nitroheterocyclic cytotoxins and radiosensitizers, the taxanes, and the vinca alkaloids, we investigated whether fenbendazole might be an agent worth testing for anticancer activity. To this end, we analyzed the effects of fenbendazole on EMT6 mammary cancer cells in culture and on solid tumors in mice. In both cases, the pharmacological properties of the drug were evaluated in combination regimens with radiation and/or docetaxel. In cell culture, intensive treatments of fenbendazole were toxic to EMT6 cells in the presence or absence of oxygen, and this toxicity increased with incubation time. In a docetaxel-inhibited tumor model in mice, 2- and 24-h treatments of fenbendazole reduced the number of surviving cells, and yield-corrected survivals were lower when fenbendazole was administered at high doses.
In vivo, 3-daily injections of fenbendazole at doses ranging from 50 mg/kg to 250 mg/kg were administered to BALB/cRw mice harboring EMT6 mammary tumors. At 10 Gy of x-ray exposure, the animals were randomized to receive three daily i.p. injections of fenbendazole (50 mg/kg/day) or pyrogen-free physiologic saline alone, and the tumors were measured at regular intervals using a colony formation assay. Treatment with fenbendazole did not alter the radiation dose-response curve in either aerobic or hypoxic tumors, and the drugs did not significantly interact when measured in a docetaxel-inhibited colony formation assay. The data provide no evidence that fenbendazole might have a clinically significant anticancer effect, despite the fact that the chemical structures of the drug have significant resemblances to those of known radiosensitizers. fenbendazole for cancer