The only known preventable cause of malignant glioma is exposure to ionizing radiation. A major goal of the Neuro-Oncology program is to conduct epidemiologic research to identify additional risk factors that can be targeted for risk reduction and brain tumor prevention. This work also studies genetic predisposition to reveal biological pathways involved in brain tumor formation and to identify high-risk populations that may benefit from enhanced brain tumor surveillance. The Data Repository and Analysis Center of the Central Brain Tumor Registry of the U.S. is directed from within the Neuro-Oncology program and provides annual reports on the incidence of primary brain tumors within all 50 states, Washington DC, and Puerto Rico.
Individual cancer cells within a single patient’s brain tumor display remarkable genetic and epigenetic differences. This “intra-tumoral heterogeneity” drives tumor recurrence and the development of therapeutic resistance. Program investigators apply cutting-edge techniques to sequence individual cancer cells in patient tumors to complement ongoing exome (DNA) and transcriptome (RNA) sequencing to reveal disease-driving genetic changes both across patients and within individual patient tumors.
For decades, Duke has been an international leader in the development of novel immunotherapies for the treatment of brain tumors, including:
- oncolytic virotherapy (e.g., poliovirus recombinants)
- dendritic cell vaccines
- other types of cell-based and antibody-based therapies
A major scientific goal is to link innate with adaptive immune responses and to harness patients’ own T cells to effectively kill tumors. From tumor-infiltrating lymphocytes to next-generation armored CAR-T cells, these cell-based approaches are designed to boost a patient’s own anti-tumor responses in order to improve clinical outcomes.
Our highest priority is the design and execution of clinical trials to help brain tumor patients experience functional improvements and lasting cures. This includes the design and execution of Phase 0, I, II, and III clinical trials with improved dose-escalation designs. It also includes Surgical Window of Opportunity (SWOOPP) studies, treating patients prior to tumor resection and collecting this tissue for further study. This yields crucial insights into a therapeutic agent’s ability to cross the blood-brain barrier and exert a biologic (i.e., pharmacodynamic) effect within the tumor.
Pre-Clinical Model Development and Biobanking
The screening of drugs and biologic agents for the identification of novel therapeutic compounds is a high priority and depends upon the development and maintenance of appropriate brain tumor models. Improved in vitro (i.e., cellular) and in vivo (e.g., mouse) models that recapitulate the behavior and molecular biology of human brain tumors are done in concert with our Brain Tumor Center Biorepository. This biorepository supports both our preclinical research and our clinical trials portfolio to identify and test novel therapies or therapeutic combinations in model systems that better reflect human disease.