Mebendazol: A novel drug to be studied for metastatic Melanoma

Most patients with metastatic melanoma fail to respond to available therapies, the discovery of a viable investigational treatment with an established safety profile is a diehard need in oncology. The prohibitive costs and long lead times typically are two requirements to discover new cancer medicines.

Effectively sidestepping these barriers, researchers at the NYU Cancer Institute and the Ronald O. Perelman Department of Dermatology promisingly screened a library of already approved drugs for activity against the most deadly form of skin cancer. They have identified mebendazole, a drug used globally to treat parasitic infections, as a novel investigational agent for the treatment of chemotherapy-resistant malignant melanoma.

The phase I clinical trial is expected to begin next year at NYU Cancer Institute. “While rational drug design remains a perfectly valid way to develop cancer therapies, we also need approaches that are less costly and more productive of new effective treatments," said lead Seth J. Orlow, M.D. Ph.D., Chair of the Ronald O. Perelman Department of Dermatology at New York University School of Medicine.

The NYU researchers screened a library of 2,000 well-known drugs and identified members of the benzimidazole family for their ability to inhibit melanoma growth and induce programmed cell death (apoptosis) of malignant melanoma cells without affecting normal melanocytes (pigment-producing cells). The team selected mebendazole, of the identified benzimidazoles, for further study because it was known to be a well-tolerated, orally available drug with anti-cancer properties.

The discovery that took the team by surprise shows that mebendazole takes advantage of a special difference between a melanoma cell and normal melanocytes. Melanomas produce high levels of a protein called Bcl-2, which is known to protect certain cancer cells from apoptosis. The team saw that when a melanoma cancer cell was exposed to mebendazole, it resulted in inactivation of Bcl-2, allowing apoptosis to occur.

Mebendazole, is sold as a generic drug and has been used since the 1970s to treat roundworm, hookworm, pinworm, whipworm, and other worm-based parasitic infections. Previous research has also shown it to have some anti-tumor activity in lung and adreno-cortical cancer.

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