Research Mission of The Preston Robert Tisch Brain Tumor Center at Duke
Malignant primary brain tumors are the most frequent cause of cancer death in children and young adults. The overarching scientific goal for the Neuro-Oncology Research Program is to develop prevention, better diagnosis, and treatment of primary malignant brain tumors in children and adults.
Our mission is:
- To conduct molecular genetic and epidemiologic studies that will identify the cause and relevant tumor suppressor and driver oncogenes in all the major types of adult and childhood malignant brain tumors. (Molecular Studies, Causation)
- To establish innovative and predictive model systems that can be used to identify accurately active and inactive therapeutic compounds prior to clinical use. (Pre-Clinical Drug Testing, Murine Models)
- To invent and translate novel therapeutics into clinical trials that incorporate innovative trial designs and techniques. (Virotherapy, Active Immunotherapy, Immunoconjugates, Clinical Trials)
- To maintain, in concert with the Duke Cancer Institute (DCI), a comprehensive brain tumor repository. (Biobanking)
- To train the next generation of neuro-oncologists—MD, PhD, and MD/PhD students; postdoctoral fellows; residents; surgical, medical, and pediatric clinical neuro-oncologists.
Research Activities and Focus Areas
The Neuro-Oncology Program at The Preston Robert Tisch Brain Tumor Center focuses its research efforts in the following areas:
Molecular Studies: The World Health Organization lists more than 126 types of brain tumors. The Neuro-Oncology Program aims to conduct full exome sequencing, copy number analysis, and other molecular studies on all the major types of adult and childhood malignant brain tumors to identify the relevant tumor suppressor and driver oncogenes of each malignant brain tumor type. New therapy based on this information will be developed, particularly against driver oncogenes. (F. Ali-Osman, S. Chitneni, Y. He, C. Kuo, H. Yan)
Pre-Clinical Drug Testing: The Neuro-Oncology Program has foundation funding to identify active and inactive compounds against more than 80 xenograft models of human malignant brain tumor types. Drugs and biologic agents are obtained from pharmaceutical and biotechnology companies and Duke Cancer Institute members, and tested in those xenograft models at no cost to the companies or investigators. This no-cost work for them is extremely important in obtaining very broad access, which is greater than usual, to new agents from those companies. (S. Keir)
Murine Models: The development of improved brain stem glioma, embryonal, and other mouse models that recapitulate the genetic alterations of the human disease to determine the function of novel drivers is an important research area. For example, a K27M histone mutation was described in 80% of high-grade brain stem gliomas in 2012, making it the most common mutation in this brain tumor subtype.
Virotherapy: The development of oncolytic virotherapy of primary and secondary CNS tumors with genetically recombinant poliovirus through basic mechanistic and clinical translational studies is a primary research effort. A broad range of research initiatives are being conducted to establish a novel form of cancer immunotherapy based on tumor targeting with poliovirus recombinants with tumor-selective cytotoxicity. (M. Gromeier)
Active Immunotherapy: The Neuro-Oncology Program has been an international leader for decades in the development of peptide vaccines, dendritic cell vaccines, and other types of cell- and antibody-based immunotherapy. A major scientific goal continues to be the development of peptide vaccines against low grade gliomas and brain stem gliomas. (J. Sampson, L. Sanchez-Perez)
Immunoconjugates: The development of monoclonal antibodies and fully human, affinity-matured antibody fragments reactive with molecular targets on primary brain tumors for diagnosis and therapy is a current goal. Immunoconjugates with new conjugation technologies for radioisotopes, such as 211Astatine and 177Lutetium, bacterial toxins, and chemotherapeutic agents suitable for treating both primary and metastatic brain tumors, as well as some systemic general cancers from other programs, are being developed. Parallel development of imaging approaches is a high priority. (D. Bigner, V. Chandramohan, G. Vaidyanathan)
Clinical Trials: An important goal and one of our highest priorities is the design and execution of Phase I, II, and III clinical trials with improved dose escalation designs for brain tumor patients. Examples of these innovative trials are genetically-modified poliovirus trials, immunotoxin trials, and peptide-based trials. Convection-enhanced delivery with innovative imaging is a high priority. (D. Barboriak, M. Bonner, T. Cummings, A. Desjardins, P. Fecci, A. Friedman, H. Friedman, H. Fuchs, J. Herndon, C. Muh, K. Peters, R. Raynor, A. Song, G. Vlahovic)
Causation: The only known external cause of malignant glioma is ionizing radiation. A major goal of the Neuro-Oncology Program is to conduct molecular genetic and epidemiology studies to identify additional causation factors so that prevention of malignant brain tumors can be implemented. Identification of a common genetic predisposition will provide information on exposures that could modify glioma risk by interaction with such genetic factors. Preventing exposure to ionizing radiation has prevented brain tumors. (D. Il’yasova)
Biobanking: The Neuro-Oncology Program continues to maintain, in concert with the DCI General Biobank, a brain tumor repository to support all of our scientific goals. (R. McLendon)