Mebendazole: Classic Antiparasitic Turned Cancer Treatment
History
Mebendazole, an FDA-approved antiparasitic drug from the early 1970s, was initially designed to treat parasitic infections—specifically those caused by intestinal worms. Its effectiveness in treating these infections is well established, but like many drugs with longstanding histories, Mebendazole is now revealing an entirely different side. Researchers are beginning to uncover its potential in treating cancer, and this discovery brings a new layer of excitement to what was once considered a conventional treatment.
Story of Discovery
The story of Mebendazole’s discovery began in the 1960s with Janssen Pharmaceutica, whose innovation brought this highly effective treatment to market in 1971. Originally celebrated for its ability to starve parasites by inhibiting glucose uptake, Mebendazole quickly became a go-to medication for common parasitic infections worldwide. Now, decades later, its unique mechanisms are taking on a different foe: cancer.
FDA Approval
Mebendazole received FDA approval in 1971 for the treatment of parasitic infections. Its initial impact was felt globally, providing an affordable and accessible treatment for helminth infections such as pinworms, roundworms, and hookworms. But as with many repurposed medications, its therapeutic potential doesn’t end with its original FDA indication.
Original Indication
This drug was originally indicated to treat parasitic worm infections in humans, operating by blocking the parasite's ability to absorb glucose, leading to its eventual death. It’s been safely used for decades, providing relief from parasitic diseases that plague many parts of the world.
Research to Repurpose
The journey of repurposing Mebendazole began as researchers took note of its effects on cellular processes beyond its original indication. In preclinical models, Mebendazole demonstrated the ability to interfere with mechanisms that are also involved in cancer progression, including microtubule disruption and apoptosis induction. These early findings paved the way for deeper investigation into its potential as a cancer therapy.
Preclinical versus Clinical Research
To date, most of the research on Mebendazole as a cancer therapy remains preclinical. This includes studies in various cancer cell lines and animal models, which have shown that Mebendazole can inhibit tumor growth and even enhance the effects of standard cancer treatments like chemotherapy and radiation. However, while the preclinical data is promising, more robust human clinical trials are needed to confirm its safety and efficacy in cancer patients. Currently, there are a few trials underway investigating its potential in aggressive cancers such as glioblastoma and triple-negative breast cancer (TNBC).
Limitations
As we often find with repurposed drugs, the excitement surrounding Mebendazole comes with challenges. One of the key limitations lies in its bioavailability when taken orally—it’s not easily absorbed into the bloodstream in its current form, which makes dosing for cancer more complex. Additionally, there are variations in how different types of cancer cells respond to the drug, and we need more human studies to determine its effectiveness across various cancer types. Nonetheless, the potential for Mebendazole to be part of a multi-faceted cancer treatment strategy remains a compelling avenue of research.
What Does the Research Show—Mechanisms?
Mebendazole is demonstrating promising anticancer effects by targeting several key mechanisms involved in cancer progression:
- Microtubule Disruption: Mebendazole binds to tubulin, a protein that forms microtubules, and prevents them from polymerizing. Microtubules are essential for cell division, so by disrupting this process, Mebendazole halts cancer cells in the G2/M phase of the cell cycle, stopping them from multiplying.
- Induction of Apoptosis: Cancer cells often evade programmed cell death, allowing them to proliferate uncontrollably. Mebendazole reactivates the mitochondrial pathway, which releases cytochrome c and activates caspases, initiating apoptosis in cancer cells, effectively reducing tumor size and spread.
- Inhibition of Angiogenesis: Tumors rely on the formation of new blood vessels (angiogenesis) to supply the nutrients and oxygen they need to grow. Mebendazole inhibits angiogenesis by downregulating pro-angiogenic factors such as VEGF, starving the tumor and limiting its ability to expand.
- Autophagy Modulation: Autophagy is a process of cellular cleanup and recycling, but in cancer cells, it can also become a survival mechanism. Mebendazole modulates this process, leading to cancer cell death by interfering with their ability to recycle critical components.
- Hedgehog Pathway Inhibition: This signaling pathway is critical in many cancers, especially those that rely on cancer stem cells for growth and survival. By inhibiting the Hedgehog pathway, Mebendazole disrupts the survival mechanisms of cancer stem cells, offering a potential strategy to prevent tumor recurrence.
- Synergistic Effects: Mebendazole enhances the effects of chemotherapy and radiation by making cancer cells more sensitive to these treatments. It works synergistically by amplifying apoptosis and autophagy, which can lead to improved patient outcomes.
Conclusion
Mebendazole is a prime example of how we can repurpose an old drug and give it new life in the fight against cancer. While it was once a staple in treating parasitic infections, Mebendazole is now at the forefront of cancer research, with early evidence showing its ability to target multiple cancer pathways. We are just beginning to scratch the surface of its potential, and as more clinical studies are conducted, Mebendazole could become a key player in personalized cancer therapy.
References
Guerini AE, Triggiani L, Maddalo M, Bonù ML, Frassine F, Baiguini A, Alghisi A, Tomasini D, Borghetti P, Pasinetti N, Bresciani R, Magrini SM, Buglione M. Mebendazole as a Candidate for Drug Repurposing in Oncology: An Extensive Review of Current Literature. Cancers (Basel). 2019 Aug 31;11(9):1284. doi: 10.3390/cancers11091284.