Researchers Create a Potential Therapy for Deadly Breast Cancer That Has Few Treatment Options
Mount Sinai researchers have designed an innovative experimental therapy that may be able to stop the growth of triple-negative breast cancer, the deadliest type of breast cancer, which has few effective treatment options, according to a study published in Nature Chemical Biology in December.
The therapy is known is MS1943. In a cancer cell line and mouse models, it degraded a protein called EZH2 that drives the growth of triple-negative breast cancer.
Research teams led by Jian Jin, PhD, Director of the Mount Sinai Center for Therapeutics Discovery, and Ramon Parsons, MD, PhD, Director of The Tisch Cancer Institute at Mount Sinai, developed MS1943 as a first-in-class small-molecule agent that selectively degrades EZH2. They also showed that agents that inhibit the enzymatic activity of EZH2 but do not degrade EZH2 did not work in triple-negative breast cancer.
MS1943 effectively reduced EZH2 protein levels in a variety of cancer cell lines, including a triple-negative breast cancer cell line, leading to the death of these triple-negative breast cancer cells.
“Our findings suggest that EZH2 selective degraders such as MS1943 may provide an emerging therapeutic approach for the treatment of triple-negative breast cancer,” said Dr. Jin, who is also Co-leader of the Cancer Clinical Investigation Program at The Tisch Cancer Institute, Mount Sinai Professor in Therapeutics Discovery, and Professor of Pharmacological Sciences, and Oncological Sciences, at the Icahn School of Medicine at Mount Sinai. “The EZH2 selective degrader reported in this study is also an invaluable tool to test therapeutic hypotheses in other cancers.”
This research was supported in part by the grants R01CA230854 and R01CA218600 from the U.S. National Institutes of Health.
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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.