�Researchers at the NYU Cancer Institute and the Ronald O. Perelman Department of Dermatology have identified mebendazole, a drug used globally to treat bloodsucking infections, as a novel investigational agentive role for the treatment of chemotherapy-resistant malignant melanoma.
Because most patients with metastatic melanoma fail to respond to available therapies, the discovery of a viable investigational treatment with an established safety profile could address a dangerous unmet indigence in oncology. Effectively sidestepping the prohibitive costs and long lead times typically required to discover new cancer medicines, the NYU team screened a library of already approved drugs for activity against the most deadly form of skin cancer.
Their report, which was selected for upgrade online publication by Molecular Cancer Research, is published in the August issue of the journal. Since submitting the article for publication, the authors possess conducted additional pre-clinical studies of mebendazole in an in vivo model of chemotherapy-resistant malignant melanoma and are now preparing a phase I clinical trial, expected to commence next class at NYU Cancer Institute.
"While rational drug design stiff a perfectly valid way to develop cancer therapies, we likewise need approaches that are less dear and more productive of new in effect treatments," aforesaid lead generator Seth J. Orlow, M.D. Ph.D., Chair of the Ronald O. Perelman Department of Dermatology at New York University School of Medicine. "You could aver this is more of a guerilla approach. Instead of screening millions of untested compounds for an agent that inhibits or stimulates a particular molecular target, we chose to screen a large library of already approved drugs for novel activity against melanoma cells, and then advance the most promising candidate apace to clinical practice."
First, the NYU researchers screened a library of 2,000 well-known drugs [Spectrum Collection (Microsource Discovery Systems)] and identified members of the benzimidazole category for their ability to inhibit malignant melanoma growth and induce programmed cell death (apoptosis) of malignant malignant melanoma cells without affecting normal melanocytes (pigment-producing cells). Of the identified benzimidazoles, the team selected mebendazole for further report because it was known to be a well-tolerated, orally usable drug with anti-cancer properties.
In a surprising discovery, the team establish that mebendazole takes vantage of a special difference of opinion 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 caspase-mediated cell death. The team saw that when a melanoma genus Cancer cell was exposed to mebendazole, it resulted in inactivation of Bcl-2, allowing apoptosis to occur.
Mebendazole, sold as a generic do drugs in the United States, has been used since the seventies to handle roundworm, hookworm, pinworm, whipworm, and other worm-based parasitical infections. Previous research has shown it to have some antitumor activity in lung and adrenocortical cancer.
"Our ability to identify novel treatments for melanoma and advance them rapidly into the clinic very much depends on NYU's multidisciplinary approach to melanoma charge and research," Dr. Orlow said. "To be effective, translational medicine cannot be unidirectional. Discovery moves endlessly back and forth between the clinic and the bench. We are now focused on determining the range of doses to be tested in the clinic, whether specific types of melanomas will respond better than others, and whether combine mebendazole with other agents will be of further benefit"
The authors of this study are NYU Cancer Institute researchers Nicole Doudican, Adrianna Rodriguez, Iman Osman, and Seth J. Orlow. The work was supported by private philanthropic grants.
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