(New York, NY - October 17, 2019) - Mount Sinai researchers have identified a targeted therapy for adolescent patients with neuroblastoma, a deadly pediatric nerve cancer, who would otherwise have no treatment options, according to a study published in October in Cancer Cell.
Neuroblastoma is one of the most common and aggressive pediatric nervous system tumors and generally has a poor prognosis, particularly when it advances in older children. Treatment success for the disease varies, but is exponentially less in adolescent patients, particularly because the disease lacks effective targeted therapies.
The Mount Sinai researchers found that neuroblastoma in older children and adolescents harboring deletions within a gene called ATRX may be responsive to a targeted therapy called tazemetostat. Tazemetostat disables an enzyme called EZH2 that inhibits genes that promote normal neuron development, in turn killing neuroblastoma cells. Neuroblastoma arises in immature nerve cells of the adrenal glands and portions of the spine during the development of the sympathetic nervous system, which controls the body's "flight or fight" response to stress. EZH2 inhibitors are already being tested in phase I and phase II clinical trials for other cancers, including lymphomas, sarcomas, and other solid tumors, with some favorable results.
"We hypothesized that mutant ATRX proteins contribute to aggressive neuroblastoma," said Emily Bernstein, PhD, Professor of Oncological Sciences at The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai and senior corresponding author. "In this study, we aimed to decipher the underlying biology of these altered proteins in neuroblastoma, a tumor for which effective therapeutic strategies remain obscure, and to exploit identified dependencies."
Mount Sinai scientists continue to expand this research into the role of the mutant ATRX protein in the laboratory and hope to eventually open a clinical trial with collaborating institutions. Based on this research, they believe that EZH2 inhibitors could also be effective in other ATRX mutant cancers, such as pediatric glioblastoma multiforme and osteosarcoma.
This work was funded by grants from the National Cancer Institute, the U.S. Department of Defense, the National Institutes of Health, and St. Baldrick's Foundation.
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. 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's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 14 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Geriatrics, Gynecology, Nephrology, Neurology/Neurosurgery, and Orthopedics in the 2019-2020 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 12th nationally for Ophthalmology and Mount Sinai South Nassau is ranked 35th nationally for Urology. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and Mount Sinai South Nassau are ranked regionally.
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