The prognosis for patients with malignant brain tumors remains grim despite advances in neurosurgery, radiation treatment, neuroimaging and chemotherapy. Clinical studies are needed to evaluate new treatment approaches. Laboratory research is required to provide the foundation for future therapies. The creation of a consortium, bringing together a multidisciplinary team of clinical and laboratory researchers and pooling the resources of several centers, will facilitate and enhance these needed studies. This proposal describes the resources available at the Pittsburgh Cancer Institute (PCI), University of Pittsburgh, qualifying it for participation in the Central Nervous System Consortium (CNSC). The Central Operations Office/Coordinating Center for this consortium will be at the University Of California, San Francisco. The resources of the PCI, including the Clinical Core Facility and the Tissue Bank, will provide essential support for CNSC-related trials. The PC Brain Tumor Center, with its clinical and laboratory investigators dedicated to advancing the treatment of brain tumor patients, will collaborate with other members of the CNSC to rapidly evaluate new treatments and investigate avenues of translational research. Initial studies will involve evaluating new agents, including taxol and temozolomide, in the treatment of malignant gliomas. Future investigations may include using inhibitors of O6-alkyl guanine DNA transferase to modulate tumor resistance to nitrosoureas, examining other investigational agents, and evaluating new drug delivery systems. Ongoing laboratory studies include exploring modulators of drug resistance, in vitro chemotherapy sensitivity assays, differentiation agents in brain tumor therapy, mechanisms of brain tumor invasiveness, and cytogenetic and molecular correlates of treatment response and prognosis. Advances in these projects will lead to innovative treatments that may be suitable for testing in the CNSC.
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