Researchers Identify Targeted Therapy That Can Help Children With Deadly Nerve Cancer
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
Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 11 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report's® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2024-2025.
For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Instagram, LinkedIn, X, and YouTube.