Neurologic Oncology Disease Management Group Research
At Perlmutter Cancer Center, the Neurologic Oncology Disease Management Group (DMG) comprises experts from our Brain Tumor Center, a world-class site for brain tumor neurosurgery and radiation oncology and a world leader in clinical, translational, and laboratory research in glioblastoma. We provide multidisciplinary, evidence-driven care for our patients based on the accurate molecular diagnosis of each brain tumor. This helps drive our clinical decisions, allowing us to determine therapeutic strategies and appropriate clinical trials.
Our neuro-oncologists, neurosurgeons, pediatric medical oncologists, radiation oncologists, neuropathologists, molecular pathologists, and neuroradiologists collaborate to focus on adult and pediatric benign and malignant brain tumors, including glioblastoma, malignant glioma, low-grade glioma, meningioma, acoustic neuroma, medulloblastoma, and central nervous system (CNS) lymphoma. We also treat spinal cord tumors, metastatic brain tumors, and neurofibromatosis, including NF1 and NF2 syndrome.
Our overarching goals are to optimize the accurate molecular and imaging diagnosis of brain tumors, discover novel therapies for malignant gliomas, improve clinical trial design for malignant glioma, and develop computer-aided technologies to resect brain tumors with the least amount of risk. Together, we determine the best treatment—such as standard therapy, clinical trials, novel surgical or radiation approaches, or novel agents—for each patient based on molecular diagnosis. Whereas other brain tumor centers use classical histopathological grading systems to make empiric treatment decisions, we diagnose and treat every patient using molecular classification, which helps us develop improved and effective therapies.
Our program members have world-recognized clinical expertise, treat a large volume of patients, maintain tissue resources and a preclinical therapeutic drug screening facility, perform interactive translational research and clinical trials, and maintain relationships with the pharmaceutical and biotechnology industries. This allows us to bring the newest and most promising therapeutic agents to our patients in the timeliest manner possible.
Members have expertise in specialized neurosurgical techniques for resection of brain tumors, intraoperative MRI, Gamma Knife® radiosurgery, laser-induced thermal therapy (LITT), molecular diagnosis, molecular and genetic profiling, and specialized imaging for brain tumors, including perfusion MRI, MR/PET, MR spectroscopy, and sodium MRI.
Our molecular neuropathologists are world pioneers in developing and implementing molecular diagnostics for brain tumors. We helped develop a method using whole-genome DNA methylation profiling and whole-genome DNA copy number profiling that has revolutionized brain tumor diagnosis by enabling accurate molecular subtyping and classification of nearly all types of brain tumors, which we perform in our Clinical Laboratory Improvement Amendments (CLIA)–certified molecular laboratory. We also use a CLIA- and New York State–certified next-generation sequencing panel to analyze DNA mutations in 580 genes known to be mutated in cancer to aid diagnosis and treatment of brain tumor patients.
Neurologic Oncology Research Leadership
John G. Golfinos, MD
Co-Director, Brain Tumor Center
Chair, Department of Neurosurgery
Associate Professor, Departments of Neurosurgery and Otolaryngology—Head and Neck Surgery
Joshua S. Silverman, MD, PhD
Assistant Professor, Departments of Neurosurgery and Radiation Oncology
Neurologic Oncology Research Areas of Focus
The Neurologic Oncology DMG focuses on malignant glioma, the most common malignant primary brain tumor. Our studies include a wide range of research, such as laboratory discovery of novel therapeutic targets and drugs, genetic and epigenetic diagnostic markers, and markers for prognosis and response to therapy.
We investigate novel imaging methods for improved noninvasive diagnostics, identify imaging features that correlate with tumor subtypes, and find novel markers in the blood. We also develop computer-aided tumor surgical methods. For glioma, we develop new radiotherapy techniques for treatment and design immunotherapy and genetic subtype–based clinical trials.
Other research areas include studies for metastatic brain tumors and neurofibromatosis. We have discovered metabolic therapies (novel NAMPT inhibitors) for the treatment of IDH-mutant and MYC amplified cancers and identified GPR133 as a therapeutic target for the treatment of glioblastoma.
In basic and translational science, we are studying the role of chromatin structure in the pathogenesis of IDH-mutant gliomas and TERT mutations in circulating cell-free DNA of malignant glioma patients. We are also researching the significance of dopamine receptor signaling in dopaminergic neurons and in K27M-mutant glioma cells and identifying novel imaging markers for molecular subtypes of glioma.
Our current clinical trials center on five key areas: improving the molecular classification of gliomas, focusing clinical trial design based on glioblastoma molecular subtypes, discovering novel imaging biomarkers that classify malignant gliomas, developing and testing immunotherapy for malignant gliomas, and discovering novel targeted stem cell and immune therapies for glioblastoma.
Previous and ongoing studies have led to advances in treatments for gliomas and glioblastomas. This includes clinical trials to study avelumab with hypofractionated re-irradiation in adults with transformed IDH-mutant glioblastoma and to test nivolumab, ipilimumab, and short-course radiotherapy in adults with newly diagnosed MGMT unmethylated glioblastoma. Other ongoing research includes studies of how H3 K27M–mutant gliomas are selectively killed by ONC201, a small molecule inhibitor of dopamine receptor D2; whether GPR133 (ADGRD1), an adhesion G protein–coupled receptor, is necessary for glioblastoma growth; and exploiting the extreme vulnerability of IDH1-mutant cancers to NAD+ depletion using NAMPT inhibitors.