Fenbendazole is a benzimidazole compound with broad antiparasitic activity in animals and is reported to have antitumor effects through binding to the microtubule-associated protein b-tubulin and disrupting its polymerization. Its use as an anthelmintic for human parasites has been limited by its toxicity and adverse effect profile. In a recent study, researchers from the National Centre for Human Genome Studies and Research (NCHGSR) at Panjab University in India have shown that fenbendazole for humans cancer may be an effective tumor suppressor.
The proliferation of cancer cells is a key factor in their resistance to anticancer therapy. To improve the effectiveness of chemotherapy, several agents have been developed that inhibit the growth of cancer cells or sensitize cancer cells to radiation or other anticancer drugs. However, it is difficult to identify the specific mechanism(s) that mediate these effects. The present study explores the antitumor and cytotoxic effects of fenbendazole, which is a broad-spectrum antihelminth agent that acts via multiple mechanisms including inhibition of microtubule formation and inhibition of RAS-related signaling.
A 80-year-old woman with advanced nonsmall cell lung cancer was started on pembrolizumab monotherapy and subsequently experienced severe liver injury 9 months later. A detailed interview with the patient and her family revealed that she had been self-administering oral fenbendazole for the past month, based on information from social media sites claiming to be effective against cancer. Following cessation of the fenbendazole, her liver dysfunction spontaneously resolved.
We used EMT6 mammary mammary tumor cells in culture and as solid tumors in mice to examine the cytotoxic and radiosensitizing effects of fenbendazole alone or in combination with the hypoxia-selective nitroheterocyclic cytotoxins and radiosensitizers, taxanes, and vinca alkaloids. In vitro, fenbendazole for humans exhibited antitumor and cytotoxic activities that were mediated by both autophagy and ferroptosis. It also induced apoptosis in 5-fluorouracil-resistant SNU-C5 cells and inhibited the formation of a pro-apoptotic complex that requires p53, suggesting that it can act as a potent radiosensitizer in p53-mutated tumors.
In a subsequent study, we determined that 10 mM fenbendazole did not significantly alter the radiation dose-response curves in both aerobic and hypoxic cultures of EMT6 cells. The relative surviving fractions were calculated from clonogenic survival data obtained by adding the drug to cultures either a few seconds or 22 h prior to irradiation and comparing the results to those of untreated controls.
We then determined the effect of fenbendazole in combination with docetaxel, a commonly used taxane, in EMT6 cell lines with different KRAS mutations. Docetaxel plus fenbendazole significantly enhanced radiosensitivity, and this was mediated by a combination of increased autophagy, augmented ferroptosis, and decreased RAS-related signaling. The data suggest that fenbendazole has the potential to be used as an additional cancer treatment in patients with a KRAS mutation and to augment the efficacy of standard therapies. The broad antiparasitic activity of fenbendazole makes it an attractive candidate for a multimodal approach to cancer therapy. However, its potential to serve as an antitumor agent for cancers with a p53 mutation needs further investigation.