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NYU researchers demonstrate activity of mebendazole in metastatic melanoma
August 07, 2008Researchers at the NYU Cancer Institute and the Ronald O. Perelman Department of Dermatology have identified mebendazole, a drug used globally to treat parasitic infections, as a novel investigational agent 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 serious unmet need 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 advance online publication by Molecular Cancer Research, is published in the August issue of the journal. Since submitting the article for publication, the authors have conducted additional pre-clinical studies of mebendazole in an in vivo model of chemotherapy-resistant melanoma and are now preparing a phase I clinical trial, 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 author 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 say this is more of a guerrilla 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 rapidly 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 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). Of the identified benzimidazoles, the team selected mebendazole for further study because it was known to be a well-tolerated, orally available drug with anti-cancer properties.
In a surprising discovery, the team found 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, sold as a generic drug in the United States, has been used since the 1970s to treat roundworm, hookworm, pinworm, whipworm, and other worm-based parasitic 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 care and research," Dr. Orlow said. "To be effective, translational medicine cannot be unidirectional. Discovery moves continuously 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 combining mebendazole with other agents will be of further benefit"
NYU Langone Medical Center / New York University School of Medicine
"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 author 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 say this is more of a guerrilla 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 rapidly 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 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). Of the identified benzimidazoles, the team selected mebendazole for further study because it was known to be a well-tolerated, orally available drug with anti-cancer properties.
In a surprising discovery, the team found 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, sold as a generic drug in the United States, has been used since the 1970s to treat roundworm, hookworm, pinworm, whipworm, and other worm-based parasitic 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 care and research," Dr. Orlow said. "To be effective, translational medicine cannot be unidirectional. Discovery moves continuously 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 combining mebendazole with other agents will be of further benefit"
NYU Langone Medical Center / New York University School of Medicine
Melanoma Current Events and Melanoma News RSSNew Notre Dame study provides insights into the molecular basis of tumor cell behavior
A new study by a team of researchers led by Crislyn D'Souza-Schorey, associate professor of biological sciences at the University of Notre Dame, sheds light on the molecular basis by which tumor cells modulate their surroundings to favor cancer progression.
Switching immunosuppressants reduces cancer risk in kidney
Switching to a newer type of immunosuppressant drug may reduce the high rate of skin cancer after kidney transplantation, according to research being presented at the American Society of Nephrology's 42nd Annual Meeting and Scientific Exposition in San Diego, CA.
Cancer survivors may not be getting the help they need to stop smoking
More than a quarter of cancer survivors who still smoke have not been advised to quit smoking by their health care providers in the last year, according to a study published by researchers at Fox Chase Cancer Center in the current issue of the Journal of General Internal Medicine.
Melanoma treatment options 1 step closer
A targeted chemotherapy for the treatment of skin cancer is one step closer, after a team of University of Alberta researchers successfully synthesized a natural substance that shows exceptional potential to specifically treat this often fatal disease.
Resident physicians seldom trained in skin cancer examination
Many resident physicians are not trained in skin cancer examinations, nor have they ever observed or practiced the procedure.
New findings on the formation of body pigment
The skin's pigment cells can be formed from completely different cells than has hitherto been thought, a new study from the Swedish medical university Karolinska Institutet shows. The results, which are published in the journal Cell, also mean the discovery of a new kind of stem cell.
Studying cancer in pet dogs to find new treatments for human patients
A team of scientists at the National Cancer Institute (NCI) in Bethesda, USA, says that studying pet dogs with cancer could yield valuable information on how to diagnose and treat human cancers.
NEDD9 Protein Supports Growth of Aggressive Breast Cancer
Researchers at Fox Chase Cancer Center have demonstrated that a protein called NEDD9 may be required for some of the most aggressive forms of breast cancer to grow. Their findings, based on the study of a mouse model of breast cancer, are presented in a recent issue of Cancer Research, available on-line now.
A potential new imaging agent for early diagnosis of most serious skin cancer
Scientists in Australia are reporting development and testing in laboratory animals of a potential new material for diagnosing malignant melanoma, the most serious form of skin cancer.
Certain cancers more common among HIV patients than non-HIV patients
Researchers at UT Southwestern Medical Center have found that non-AIDS-defining malignancies such as anal and lung cancer have become more prevalent among HIV-infected patients than non-HIV patients since the introduction of anti-retroviral therapies in the mid-1990s.
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