Molecular Therapeutics for Anaplastic Gliomas

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In spite of over thirty years of effort, the prognosis for patients afflicted with malignant gliomas remains dismal. It is the purpose of this Brain Cancer SPORE to have a positive impact on this unacceptable situation by translating the laboratory-based efforts of five groups of scientists into clinical protocols that address the needs for more effective treatments. The themes that will be investigated in this SPORE include: Pathogenesis, Anti-Invasion Strategies, Glioma-Host Interactions, Viral and Gene Therapy, and Anti-Angiogenesis Strategies. Five research projects are proposed, each of which has a translational component that has or is expected to lead to a clinical research protocol. These include: 1) "The role of Human Cytomegalovirus in Human Malignant Glioma Pathogenesis" which will examine an intriguing finding that suggests that cytomegalovirus promotes the development and progression of gliomas; 2) "Interferon-Mediated Suppression of MMP-9 Gene Expression and Function in Gliomas" which will examine the role of cytokines and signal transduction pathways in regulating secretion of a pro-invasive enzyme; 3) "Ion Channels and Transporters as Novel, Glioma-specific Targets", which will examine how abnormal functioning of glioma ion channels can be potentially manipulated to develop new treatment modalities, 4) "Viral and Molecular Chemotherapy of Malignant CNS Tumors", which will utilize the extensive expertise in virology available at UAB to development new gene and viral vector therapies for gliomas, and 5) "The Role of TSP-1 and -2 in the Biology of Gliomas", which will investigate how to utilize fragments of the protein thrombospondin as anti-angiogenic agents. These projects will be supported by Four Cores: 1) Human Brain Tumor Tissue, 2) Clinical Trials; 3) Brain Tumor Animal Core Facility; and 4) Biostatistics. In addition, the SPORE will have a Career Development Program directed at developing the careers of young investigators in brain tumor translational research and a Developmental/Pilot Research Program. This SPORE has strong institutional commitments from both the University and its Cancer Center, and we fully expect to develop active collaborative interactions with both our institutional SPOREs as well as with other SPOREs nationally.