Targeting the Microenvironment of Glioblastoma to Block Tumor Progression

Glioblastoma (GBM) is a devastating malignant brain tumor that defies surgical resection and traditional therapies. Despite the advances in GBM management, patient survival is dismal because there are no effective therapies. Recent efforts examined targeting cells other than GBM cells, mainly immune cells, as a potential treatment for GBM, but this approach was ineffective. This may be due to the nature of the cells that reside in the periphery of the tumor resected by the neurosurgeon (resection margin), which consists of few tumor cells and immune cells, and many neurons and astrocytes. Astrocytes are the major support cells in the brain that maintain the health and function of other brain cells. Evidence suggests that astrocytes contribute to GBM spread and growth. My preliminary data suggests molecules that come from astrocytes can promote GBM progression. In this study, I hypothesize that eliminating these molecules, and thereby blocking the interaction between the astrocytes and GBM cells, will lead to reduced GBM spread, increased GBM cell death, and may make GBM more vulnerable to therapy. I will test this hypothesis in animal models of GBM, patient derived GBM tissue, and cellular models of GBM using a combination of cutting-edge molecular studies designed to test GBM cell function and gene expression. My project has the potential to uncover novel therapies for GBM based on targeting astrocytes and may provide neurooncologists with additional tools to combat GBM.