Fenbendazole for humans is a drug in the benzimidazole carbamate family of broad-spectrum anthelmintics that has been in clinical use for about six decades. It is used to treat a wide range of gastrointestinal parasites, including giardiasis, roundworms, hookworms, whipworms, pinworms, and the Taenia genus of tapeworms.
The anthelmintic effect of fenbendazole is primarily based on its ability to inhibit microtubule polymerization. Microtubules are important structures that support cell division. They are responsible for lining up the chromosomes at metaphase and then separating them evenly during anaphase to allow them to be distributed into each of the two daughter cells. Fenbendazole and other drugs in the benzimidazole family, such as albendazole and mebendazole, interfere with microtubule formation. This leads to the blockage of cell division, and thus the death of the parasites that depend on it for survival. It is also thought that the interference with microtubules may have antitumor effects, but this has not been proven yet.
In the present case, a 57-year-old woman with advanced NSCLC was taking pembrolizumab monotherapy when she developed a grade III liver injury that required hospitalization. Her CEA levels had increased, and she was afraid that the cancer was progressing. She purchased and started taking oral fenbendazole, a benzimidazole compound that is marketed as an anthelmintic for dogs, based on information she found on social media sites that stated it had antitumor activity.
Unlike some other anticancer agents, fenbendazole is not associated with a hypersensitivity reaction in patients. In vitro and in vivo studies of fenbendazole have shown that it is effective against human cancers, including those with KRAS mutations. In one study, fenbendazole reduced tumor growth in a mouse lung adenocarcinoma model with a KRAS mutation, and it also inhibited RAS-related signaling pathways.
In the present study, we showed that fenbendazole caused G2/M arrest and apoptosis in 5-FU-sensitive and 5-FU-resistant SNU-C5 colorectal carcinoma cells. The apoptosis induced by fenbendazole was partially due to activation of p53, and it was augmented by autophagy and ferroptosis. Furthermore, fenbendazole suppressed the expression of LC3, Atg7, and GPX4 in 5-FU-resistant SNU-C5 cells. These results suggest that fenbendazole could be a novel therapeutic agent for 5-FU-resistant cancers.
