This Duke Brain Tumor SPORE grant consists of four projects, five cores, a Developmental Research Program, and a Career Development Program. The goal of the proposed research is to advance knowledge of brain tumor biology and etiology and to translate these into clinical protocols that represent significant and novel advances in the management of these therapeutically intractable tumors. The grant, as a whole, and each project and core, are led by basic and clinical Principal Investigators. In Project 1, novel therapeutics that target the GSTP1 protein, overexpressed and a poor prognostic indicator in malignant gliomas, will be rationally developed and evaluated for clinical efficacy. Project 2 will investigate novel molecular mechanisms of resistance of CNS tumors to Temodar, a clinically active brain tumor agent and evaluate the clinical efficacy of a PARP inhibitor in reversing Temodar resistance. Project 3 will investigate dendritic cell-based vaccination against CMV as a therapeutic modality in malignant glioma and the underlying mechanisms of the anti-tumor response. In Project 4, molecular and epidemiologic studies will examine the etiology of brain tumors in a case-control study. Exposure to putative neurocarcinogens will be examined and polymorphisms in metabolism and DNA repair genes will be examined as a determinant of brain tumor risk and treatment-associated toxicity. The cores include a Tissue Procurement and Genetics Core, an Investigational New Drug Permit Core, a Phase I/II Clinical Trials Core, a Biostatistics and Information Systems Core, and an Administrative Core which will provide critical infrastructural and service functions. The Developmental Research Program will consist of pilot projects identified from the entire Cancer Center membership at Duke as well as from selected, outside institutions. Emphasis is on investigators who have not previously worked in neuro-oncology. Nine examples of pilot projects from senior investigators at Duke who have not previously worked on brain tumors are included.
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