The treatment of stage 4 cancer is often a long journey and involves a combination of therapies. The type of therapy will depend on the stage of cancer, a patient’s overall health, and several other factors. While the cancer itself isn’t usually curable, treatments can significantly improve quality of life and prolong survival.
The benzimidazole anthelmintic agent fenbendazole (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl) carbamate) is used as an antiparasitic agent in several animal species, and has been repurposed for cancer treatment due to its broad spectrum, high safety margin, and low cost5. The drug has been shown to inhibit microtubule-associated tubulin polymerization and induce cell death, with higher efficacy than albendazole in 5-fluorouracil-resistant colorectal cancer cells[6].
However, the mechanism of fenbendazole’s antitumor effects remains unclear. A recent report described an 80-year-old woman who suffered from genitourinary malignancies and self-administered fenbendazole after obtaining information on social media on its antitumor activity[9]. She later developed severe liver injury, and her condition became worsened.
Our data show that fenbendazole increases the viability of wild-type but not mutant p53-driven SNU-C5 colorectal cancer cells and induces G2/M arrest and apoptosis. In addition, the drug also induces autophagy and ferroptosis in 5-FU-resistant cells. The activation of necroptosis is dependent on the phosphatidylation and activation of caspase-8 by RIP1 and RIP3 kinases, which then leads to MLKL phosphorylation. Thus, fenbendazole’s induction of autophagy and ferroptosis could be the key to its antitumor activities. Moreover, the drug enhances the cytotoxicity of radiation and 5-FU against 5-FU-resistant CRC cells, which may be attributed to its inhibition of multidrug resistance. fenbendazole cancer