In a Race to Cure Childhood Brain Cancer, Leading Experts Unveil the Mount Sinai Children’s Brain and Spinal Tumor Center

New York, NY August 1, 2022) –  In a race against time to cure childhood brain cancer, the leading cause of cancer deaths among children, Mount Sinai Kravis Children’s Hospital is forming the Mount Sinai Children’s Brain and Spinal Tumor Center. The center is being propelled forward by a series of generous grant awards to three of its scientists, all leaders in the field of childhood brain cancer. It will be housed within Mount Sinai Kravis Children’s Hospital.

A $3.33 million National Institutes of Health (NIH) Research Project Award, known as an R01, from the National Cancer Institute will fund the researchers’ investigation into the role of myeloid cells in a type of pediatric brain cancer known as high-grade glioma. These gliomas are described as “high grade” because they are fast growing and spread quickly throughout the brain, making them extremely difficult to treat. They are considered somewhat rare, comprising approximately 10 percent of childhood brain cancers. Dolores Hambardzumyan, PhD, Associate Professor, Oncological Sciences, and Oren J. Becher, MD, Chief of the Jack Martin Fund Division of Pediatric Hematology-Oncology, the Steven Ravitch Chair in Pediatric Hematology-Oncology, and Professor of Pediatrics at the Icahn School of Medicine at Mount Sinai, will be the Principal Investigators. The grant will be effective through May 31, 2027. In addition, a $483,000 NIH Exploratory/Developmental Research Grant (R21) award will fund Dr. Hambardzumyan’s work to better understand and overcome immunotherapy resistance in pediatric high-grade glioma. This award will be effective through November 17, 2023.

“We greatly appreciate these two awards at a time when we are racing for a cure. The NIH R01 grant will support our investigation into myeloid cells, which we view as highly important. We hypothesize that myeloid cells, which comprise up to 30 percent of the cells in high-grade gliomas, are important in tumor promotion and resistance to therapy, including immunotherapy, which is a primary focus of the NIH R21 grant. We will look to identify new treatment strategies to treat pediatric high-grade glioma by targeting molecules secreted by these myeloid cells,” says Dr. Hambardzumyan.

“With Dr. Hambardzumyan’s expertise in myeloid cells in gliomas and my own background studying pediatric high-grade gliomas, we can combine and complement our expertise to dissect the role of myeloid cells in pediatric high-grade gliomas,” says Dr. Becher.  

“There are several subtypes of high-grade gliomas in children. One of them, diffuse midline glioma (DMG), is driven by an abnormal histone protein (H3K27M). Histone proteins are proteins in the cells that help package the genetic code inside the nucleus, in addition to determining which genes are turned on or off inside cells. This type of tumor is currently incurable,” says Dr. Becher. He notes that most children only survive about 12-15 months when they receive the standard of care, which is focal radiation.

In recent months, Dr. Becher has published two important papers exploring the pathogenesis of DMG. In a paper published in GLIA in May 2022, Dr. Becher describes a novel model of DMG initiated in oligodendrocyte progenitor cells, a cell type implicated as the cell of origin for DMG. Surprisingly, the authors note that the abnormal histone protein, H3K27M, did not promote cell growth in this model. These findings contrast with their prior DMG model initiated in stem cells in the brain. The only consistent effect of the abnormal histone protein across both models was inhibition of immune system activation by the abnormal histone protein. These findings suggest that it will be challenging to successfully treat DMGs with therapies that aim to activate the immune system against the cancer cells without also blocking the abnormal histone protein. This work was funded by another NIH R01 as well as K02 and R21 NIH grants previously awarded to Dr. Becher with Dr. Hambardzumyan as a study collaborator.

In addition, in a paper published in BMC in April 2022, Dr. Becher studied the role of an enzyme called enhancer of zeste homolog 2 or EZH2 in DMG. “As EZH2 inhibitors are now FDA-approved for treatment of cancers such as epithelioid sarcoma, and have been suggested as a potential therapy for DMG, we wanted to study the role of EZH2 in DMG. Interestingly, our work provides a strong indication that EZH2 may act as a tumor suppressor during early stages of DMG tumor formation, suggesting more careful investigation is needed in the translation of EZH2 inhibitors to treat DMG,” says Dr. Becher. Praveen Raju, MD, PhD, Associate Professor of Neurology, and Pediatrics, at Icahn Mount Sinai was a collaborator on this work, which was funded by the American Cancer Society.

Along this collaborative theme, Dr. Raju and Dr. Becher were recently awarded a ChadTough Defeat DIPG Foundation Game Changer Grant of $600,000, which will support their research into diffuse intrinsic pontine glioma (DIPG), a DMG subtype localized to the pons, a part of the brain stem. They will evaluate a novel nanomedicine platform to enhance drug delivery past the blood-brain barrier, which remains an enduring obstacle to effective treatment for DIPGs. For more than a decade, Dr. Becher has focused on identifying therapeutic targets to treat DIPG, contributing some of the seminal discoveries in the DIPG field since he began studying this puzzling cancer in 2008. Dr. Becher developed the first animal model of DIPG, considered a crucial step in understanding the disease and how to treat it.

Dr. Raju is best known for his translational research developing novel genetic mouse models of medulloblastoma, the most common type of malignant pediatric brain cancer, and he and his collaborators have recently advanced a new nanotherapeutic technology for enhancing drug delivery past the blood-brain barrier that synergizes with radiation, the primary treatment modality for most pediatric brain tumors. Dr. Hambardzumyan’s expertise in neuroimmunology in both pediatric and adult tumors further complements the programmatic research foundation as the three scientists work to find a cure.

“Pediatric brain tumors are now the leading cause of cancer-related death in children. And yet, funding for these devastating childhood tumors has been historically very low compared to other pediatric and adult cancers. The recent success in obtaining these highly competitive federal and national foundation grants is a testament to the innovative and collaborative pediatric brain tumor-related research that is ongoing within the laboratories of Dr. Becher, Dr. Hambardzumyan, and Dr. Raju. These three leaders are all recent recruits brought on to accelerate our momentum toward a greater understanding of childhood cancer and, ultimately, to improve the outcomes of these children for whom we are fighting so hard,” says Fernando Ferrer, MD, Chief Operating Officer of Mount Sinai Kravis Children’s Hospital, Vice Chair of Hospital Operations in the Department of Pediatrics, and Network Medical Director for Pediatric Services for the Mount Sinai Health System 

Drs. Becher and Raju will serve as Co-Directors of the Mount Sinai Children’s Brain and Spinal Tumor Center together with Saadi Ghatan, MD, a neurosurgeon who treats neonates, children, adolescents, and adults for nervous system conditions of the head, brain, spinal cord, and peripheral nerves. An expert in minimally invasive neurosurgery with endoscopy, epilepsy, and brain mapping with electrophysiological monitoring, Dr. Ghatan is Professor of Neurosurgery, and Pediatrics, at Icahn Mount Sinai, Chair of Neurosurgery at Mount Sinai West and Mount Sinai Morningside, and Director of the Health System’s Pediatric Neurosurgery Program. Dr. Ghatan partners with Peter F. Morgenstern, MD, a pediatric neurosurgeon who brings novel expertise in the management of tumors of the skull base in children, with neuroendoscopic methods. Together, Drs. Ghatan and Morgenstern bring expertise and access to state-of-the-art surgical services using navigation, laser ablation, fluorescence-guided tumor resection, and intraoperative MRI accessibility.

Visit the Children’s Brain and Spinal Tumor Center | Icahn School of Medicine (mssm.edu) online for more information.

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 more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 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 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report’s Best Hospitals, receiving high “Honor Roll” status, and are highly ranked: 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. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children’s Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently 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 top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. 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. For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter, and YouTube.