Mount Sinai Researchers Discover Epigenetic Reason for Drug Resistance in a Deadly Melanoma
Also Identify Potential Therapies to Prevent Drug Resistance
Mount Sinai researchers have discovered a previously unknown reason for drug resistance in a common subtype of melanoma, one of the deadliest forms of cancer, and in turn, have found a new therapy that could prevent or reverse drug resistance for melanoma patients with a particular gene mutation, according to a study published in Nature Communications.
The researchers identified a novel epigenetic mechanism that causes resistance to the standard treatment in melanoma patients with mutations in the BRAF genes, which are found in about half of all melanomas. Researchers also found a biomarker, or a biological signature that accompanies this drug resistance: a gene called IGFBP2, which is also associated with poor prognosis in melanoma patients.
Patients with high levels of IGFBP2 could benefit from combination therapies, which could be created in response to these findings, that inhibit BRAF mutations and IGFBP2-driven biological pathways as a multi-pronged approach to preventing drug resistance or reversing it once it has occurred, the study shows. Other studies show the potential to find IGFBP2 via urine samples so the implications for detection and later treatment are large.
“The incidence of cutaneous malignant melanoma is rising and its therapeutic management remains challenging,” said lead researcher Emily Bernstein, PhD, Associate Professor of Oncological Sciences and Dermatology at the Icahn School of Medicine at Mount Sinai. “In recent years, there has been extensive therapeutic development to inhibit key biological targets. Although a large proportion of patients with advanced metastatic melanoma harboring BRAF mutations respond to the standard therapy, known as MAPK inhibitors, subsequent resistance remains a major clinical challenge.”
This research was funded by La Roche-Posay North American Foundation, American Skin Association, Pershing Square Sohn Cancer Research Alliance, and the U.S. Department of Defense.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai advances medicine and health through unrivaled education and translational research and discovery to deliver care that is the safest, highest-quality, most accessible and equitable, and the best value of any health system in the nation. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture ambulatory surgery centers; more than 415 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. The Mount Sinai Hospital is ranked on U.S. News & World Report's "Honor Roll" of the top 20 U.S. hospitals and is top in the nation by specialty: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. Mount Sinai Kravis Children's Hospital is ranked in U.S. News & World Report’s “Best Children’s Hospitals” among the country’s best in four out of 10 pediatric specialties. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools," aligned with a U.S. News & World Report "Honor Roll" Hospital, and No. 14 in the nation for National Institutes of Health funding. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.