Glioblastoma multiforme is a highly lethal cancer for which conventional therapies such as surgical resection, irradiation therapy and systemic chemotherapy are essentially palliative. Recently, results from several laboratories have suggested that cancer stem cells, also referred to as tumor-initiating cells, may be important determinants of the overall behavior of glioblastomas. After surgical resection, in-situ brachytherapy speci_cally directed against cancer stem cells and their dysregulated cellular machinery may be more e_ective in controlling glioblastoma growth than today's unselective therapeutic strategies. Therefore, we intend to design methods to speci_cally sort out cancer stem cells or cells particularly prone to invasiveness from surgical glioma specimens. Second, we plan to subject these cells to a thorough phosphoproteomic pro_ling using high density protein arrays that allow us to determine an individual status of activated / deactivated phosphoproteins in the pool of tumor-initiating cells at the time of resection compared to reference tissue. Furthermore, we intend to streamline this process in order to provide a molecular signature within a week after bulk tumor resection in order to potentially design patient-tailored drug regimens (i.e. kinase inhibitors, RNA-interference) that could be administered through specialized catether systems into the resection cavity.
