In the present study, we sought to (1) evaluate in situ protein expression of HIF2α in gliomas, (2) link increased HIF2α expression to hypoxia in glioblastoma cells in vitro and test the effect of a clinically available HIF2α inhibitor, PT2385, on cell survival and proliferation, and (3) explore the activity of PT2385 as a single agent and then in combination with standard of care chemoradiotherapy for GBM. The gene discussed is EPAS1; the disease is central nervous system cancer.