Mebendazole: An Antiparasitic with Cancer-Fighting Potential

Mebendazole is an antiparasitic drug first approved by the FDA in 1971, initially used to treat parasitic infections such as intestinal worms. In 2002, researchers began exploring its anticancer potential, discovering it induced apoptosis in cancer cells by disrupting tubulin polymerization. Despite promising early results, mebendazole was withdrawn from the U.S. market in 2011 due to manufacturing issues but reintroduced in 2016 at a significantly increased price—from $5.82 per tablet in 2010 to $508.07 per tablet in 2019. (Could the results as a promising cancer drug have anything to do with the price increase?) (1,2)

How Mebendazole Works Against Cancer

Mebendazole is FDA-approved for human use, primarily for parasitic infections. Its anticancer effects arise from several mechanisms:

• Disrupts tubulin polymerization, critical for cell division
• Inhibits angiogenesis, preventing tumor blood supply
• Induces apoptosis through activation of caspases and cytochrome c
• Suppresses hypoxia-inducible factors (HIF-1α and HIF-2α), which are critical for tumor survival under low oxygen conditions

These combined actions effectively halt tumor growth and reduce metastatic potential, making it a promising candidate for cancer therapy.

Cancers Showing Promise with Mebendazole (3,4)

• Pancreatic cancer
• Lung cancer
• Thyroid cancer
• Breast cancer
• Colorectal cancer
• Brain tumors (glioblastoma and medulloblastoma)

Ivermectin: Another Promising Antiparasitic

Ivermectin is another FDA-approved antiparasitic medication initially developed to treat parasitic infections like river blindness. It shows promise in enhancing mebendazole's anticancer effects through several mechanisms:

• Inhibits Akt/mTOR signaling pathways that promote cancer cell survival
• Induces apoptosis by increasing reactive oxygen species (ROS) production
• Reverses multidrug resistance, enhancing chemotherapy effectiveness
• Suppresses angiogenesis, reducing tumor blood supply

Cancers Showing Promise with the Ivermectin-Mebendazole Combination (5,6)

• Colorectal cancer
• Breast cancer
• Ovarian cancer
• Melanoma
• Leukemia
• Pancreatic cancer

Safety Profiles of Mebendazole and Ivermectin

Mebendazole

Mebendazole exhibits a favorable safety profile with generally low toxicity. Clinical studies report that doses up to 4 grams per day are well-tolerated without severe adverse effects. Common mild side effects include nausea, abdominal pain, decreased appetite, and vomiting. However, caution is advised when combining mebendazole with certain chemotherapy agents such as lomustine due to increased risks of anemia and fatigue at higher doses. Contraindications include hypersensitivity to benzimidazoles and caution in pregnant patients due to potential teratogenic effects. (2,7)

Ivermectin

Ivermectin also has a favorable safety profile, even at high doses, with clinical studies consistently reporting it as safe and well-tolerated. A meta-analysis involving 18 trials and 2,496 participants found no significant differences in adverse events between ivermectin and control groups, indicating minimal risk of serious side effects across various dosing regimens. Contraindications include pregnant women, children under 5 years, and caution in persons with CNS disorders. Like mebendazole, side effects are usually mild, including nausea, diarrhea, vertigo, and loss of appetite. (8,9)

Targeting Multiple Cancer Pathways

The synergistic effects of mebendazole and ivermectin could significantly enhance therapeutic outcomes by simultaneously targeting multiple cancer pathways, reducing chemoresistance, and limiting metastatic spread. Given their established safety profiles and cost-effectiveness compared to traditional chemotherapy agents, these repurposed antiparasitic drugs represent a major advancement in cancer care.

References

1. Pantziarka, P., Bouche, G., Meheus, L., Sukhatme, V., & Sukhatme, V.P. (2014). Repurposing Drugs in Oncology (ReDO)-mebendazole as an anti-cancer agent. Ecancermedicalscience, 8, 443.
2. Krystal, J., Hanson, D., Donnelly, D., & Atlas, M. (2024). A phase 1 study of mebendazole with bevacizumab and irinotecan in high-grade gliomas. Pediatric Blood & Cancer, 71(4), e30874.
3. Williamson, T., Bai, R.Y., Staedtke, V., Huso, D., & Riggins, G.J. (2016). Mebendazole disrupts microtubule formation and inhibits angiogenesis in colorectal cancer xenografts. Oncotarget, 7(42), 68571–68584.
4. Joe NS, Wang Y, Oza HH, Godet I, Milki N, Riggins GJ, Gilkes DM. Mebendazole Treatment Disrupts the Transcriptional Activity of Hypoxia-Inducible Factors 1 and 2 in Breast Cancer Cells. Cancers (Basel). 2023 Feb 20;15(4):1330.
5. Juarez, M., Schcolnik-Cabrera, A., & Dueñas-Gonzalez, A. (2018). The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug. American Journal of Cancer Research, 8(2), 317–331.
6. Dou Q, Chen HN, Wang K, et al. Ivermectin Induces Cytostatic Autophagy by Blocking the PAK1/Akt Axis in Breast Cancer. Cancer Res. 2016 Aug 1;76(15):4457-69.

Written By: Brooke Lounsbury