This SPORE renewal application represents the efforts of interdisciplinary teams of investigators from the Neuro-Oncology Program of the UCSF Comprehensive Cancer Center to apply their knowledge and expertise to translational research focused on brain tumors. The heart of the application is five translational research projects, each driven by teams of applied and basic investigators, and each intended to create novel tools and therapies useful in the treatment of brain tumors. Project One is an extension of a highly successful population science project that intends to define factors important in glioma patient survival. Project Two is an extension of a highly successful imaging project that intends to use sophisticated spectroscopic techniques to non-invasively define factors that predict low-grade glioma biology. Project Three builds on novel drug-containing lipidic nanoparticles developed in the previous funding period, and proposes to generate and test new therapeutic nanoparticles whose distribution can be controlled by convection-enhanced delivery and monitored in real time spectroscopically. Project Four proposes lab based and clinical studies intended to clarify and exploit the negative association discovered in the previous funding period between Akt activation and sensitivity to the EGFR inhibitor erlotinib. Project Five, which evolved from the convergence of two Developmental Research Projects in the previous funding period, proposes lab-based and clinical studies intended to investigate and exploit the role the PTEN/Akt/mTOR pathway plays in response to glioma vaccine therapy. The application also requests continued support for highly successful Career Development and Developmental Research Programs, and for four Cores (the existing Tissue and Administrative Cores and the new Animal and Biostatistics/Clinical Core) that will support all aspects of the work. Each project draws on the extensive experience of the investigators in brain tumor research, and on the long history of translational brain tumor research in the UCSF Department of Neurological Surgery and UCSF Brain Tumor Research Center. The projects will be additionally strengthened by collaborations with scientists in the UCSF Comprehensive Cancer Center and in the UCSF Breast and Prostate SPOREs. Finally, as a leading center of brain tumor clinical trials in America, an infrastructure is in place in the UCSF Neuro-Oncology Program to allow rapid clinical translation of important scientific discoveries. The Principal Investigator of the UCSF Brain Tumor SPORE is Mitchel Berger, MD, a nationally recognized leader in neurosurgery and translational brain tumor research. The clinical co-PI of this application is Michael Prados, MD, the PI of the North American Brain Tumor Consortium and a recognized leader in the development and implementation of clinical trials in brain tumors. The basic science co-PI of this application is Russell Pieper, PhD, the Basic Science Director of the UCSF Neuro-Oncology Program and the UCSF Brain Tumor Research Center and a recognized leader in the study of cell signaling in gliomas. The combined administrative, clinical, and lab-based experience of the leadership team, along with the strong interdisciplinary research teams and the strong research climate at UCSF suggest that the work proposed will lead to significant progress in the treatment of brain tumors.
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