Microenvironmental regulation of glioblastoma radiosensitivity

Division Of Basic Sciences - Nci

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Abstract

Towards generating novel insights into the radiobiology of GBM, studies using GSC-initiated xenografts focused on this radioresistant subpopulation. Along these lines, an aim of this research is to identify the mechanisms and processes responsible for the radioresistance of tumor cells in the olfactory bulb (OB). Also the role of this radioresistant subpopulation in the radiation-driven evolution of GSC orthotopic xenografts was examined. These studies should generate insight into the fundamental biology and treatment response of recurrent GBMs. Finally, we continue to use GSC-initiated xenografts as a preclinical model for testing strategies aimed at improving GBM response to radiotherapy. Agents to be evaluated will be those targeting the proteasome. Moreover, to further understand the impact of the OB radioresistant niche, the effects of targeted agents on the radiosensitivity of glioma cells in the OB will be determined. Consistent with the goals of the ROB, this project, in addition to fundamental information, should provide a source of targets for primary and recurrent GBM radiosensitization.