A deworming medication for dogs that’s also used to treat parasites and worms in humans, fenbendazole, is receiving attention from people with cancer thanks to claims that it can cure the disease. This is based on the anecdotal story of Joe Tippens, who claimed that he was cured of lung cancer by taking fenbendazole and other supplements, a regimen that became known as the “Joe Tippens protocol.” But while there are some indications that fenbendazole might be effective against cancer cells in petri dishes and mice, there’s no evidence it will cure human cancer, and there’s plenty of reason to be skeptical of such claims.
Benzimidazole drugs like fenbendazole (FZ) act through multiple cellular pathways, including inhibition of cell cycle progression. They disrupt microtubule dynamics, bind to tubulin and inhibit its assembly, and bind to cyclin B1 to prevent its interaction with cyclin-dependent kinase 1 (CDK1), thereby arresting the cell in metaphase and inducing mitotic catastrophe. In addition, they inhibit phosphorylation of key glycolytic enzymes and reduce glucose uptake in the cells.
Cancer cells have a high metabolic requirement for energy, and they take up glucose to meet this demand. To investigate whether FZ can affect glucose metabolism in cancer cells, we treated H460 and A549 cancer cells with varying concentrations of FZ for 4 h. We found that treatment with increasing concentrations of FZ resulted in a decrease in glucose uptake, measured using the fluorescent glucose analogue 2-NBDG. Additionally, FZ treatment resulted in reduced glucose oxidation, as measured by the production of lactate in the cells.
A pharmacokinetic study showed that FZ and RAPA were well encapsulated in mPEG-b-PCL, and the mPEG-b-PCL micelles accumulated at a higher concentration in the livers, spleens, hearts, kidneys, and lungs than the solution formulations. In vivo pharmacokinetic studies in mice showed that both the solution and micelle formulations of FEN/RAPA had similar efficacy, with AUC0- 2 h and AUC0- 8 h values comparable to those of the free drugs in the mice.
To determine the antitumor activity of the drug combination, mice with EMT6 tumors were randomized to receive three i.p. injections of fenbendazole or to receive 10 Gy of radiation plus fenbendazole. Mice receiving fenbendazole alone showed no significant effect on tumor growth or radiation response, but mice receiving the FZ/RAPA combo demonstrated significantly improved survival. The authors speculate that the pleiotropic effects of FZ and RAPA together may account for the observed synergistic effect on cancer cell viability, with inhibition of multiple pathways contributing to the overall effect. This is particularly important, as single-target drugs often show limited efficacy and can lead to resistance13. The results of this work suggest that FEN/RAPA can be a novel approach to treating human cancers. However, further studies will be necessary to establish the optimal dose and delivery method for fenbendazole/RAPA conjugates in a clinical setting. fenben for cancer