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High-grade gliomas are among the deadliest of all cancers despite standard treatments, and new therapeutic strategies are needed to improve patient outcome. Targeting the altered metabolic state of tumors with traditional chemotherapeutic agents has a history of success, and our increased understanding of cellular metabolism in the past 2 decades has reinvigorated the concept of novel metabolic therapies in brain tumors. Here we highlight metabolic alterations in advanced gliomas and their translation into clinical trials using both novel