Fenbendazole is an inexpensive and commonly used benzimidazole anthelmintic that has broad antiparasitic activity in dogs and pigs, as well as a wide range of gastrointestinal parasites including pinworms, giardia, roundworms, hookworms, and Taenia solium. Recently, it has been reported to exert antitumor effects in cultured cancer cells. However, the mechanisms of its activity remain largely unknown. A recent study by Johns Hopkins researchers suggests that it may act to inhibit tubulin polymerization, thus starving cancer cells of their microtubules, an essential process in cell division. The study was funded by the Virginia and D.K Ludwig Fund for Cancer Research.
In an earlier meeting presentation (19), the team showed that high doses of fenbendazole, albendazole, and mebendazole effectively inhibited the growth of human colon cancer cells and patient-derived colon cancer organoids. They also found that fenbendazole significantly augmented the cytotoxicity of paclitaxel in paclitaxel-resistant colorectal cancer cells, suggesting that it could be a promising combinatorial therapy agent with paclitaxel.
To test the efficacy of fenbendazole as an antitumor agent in vivo, the scientists tested its effect on EMT6 tumors that had been irradiated to induce hypoxia. They compared the growth of these tumors with that of unirradiated EMT6 tumors and those treated with three daily i.p. injections of fenbendazole or with 10 Gy of x-ray radiation. The results showed that the growth of irradiated tumors was not inhibited by fenbendazole alone, but that the drug was synergistic when combined with x-rays (Figure 3).
Moreover, to assess whether fenbendazole might have direct antitumor activity, the investigators measured the cellular response to docetaxel using a rigorous colony formation assay. When a 2-h incubation with high concentrations of fenbendazole was added to the docetaxel dose-response curve, the result was a dramatic reduction in the surviving fraction relative to controls; 24-h treatment with the drug reduced the surviving fraction to 0.18+-0.02 percent.
Finally, to determine if fenbendazole might directly target mitosis and inhibit cancer cell proliferation, the investigators measured the levels of the cyclin B1 kinase in A549 cells. The cyclin B1 kinase is required for progression through metaphase to anaphase, and its activity is inhibited by the proteasome-mediated degradation of ubiquitin-linked CDK1 complexes. They found that fenbendazole directly inhibited the phosphorylation of the cyclin B1 kinase and induced cell-cycle arrest.
To examine whether the information on fenbendazole’s potential antitumor effects that was disseminated through social media was accurate, the scientists surveyed a number of patients who had acquired such information. Only two of the 21 participants indicated that they were aware that Joe Tippens, who first presented the findings on YouTube, was himself undergoing other treatments for his own cancer. The authors conclude that the information that patients receive through social media is often inaccurate and should be actively cross-checked to identify the source of the information and the validity of its content. Byunghak Kang, Byung-Sun Kim, Cory Brayton, Thais Biude Mendes, and Paulo Pimentel de Assumpcao, all from Johns Hopkins University, report in the journal Cancer Discovery that the benzimidazole anthelmintic mebendazole inhibits tubulin polymerization, thereby starving cancer cells of their microtubules, which are critical for cell division. fenbendazole cancer