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Resistance to chemotherapy and radiotherapy is both intrinsic and acquired: the blood-brain barrier makes delivery of chemotherapeutic drugs to neoplastic cells difficult, and GBM itself is molecularly heterogeneous and often features robust DNA repair mechanisms such as enhanced methylated-DNA-protein-cysteine methyltransferase (MGMT) activity ( This review examines the metabolic landscape of GBM, with a focus on the widespread reprogramming of energy pathways that enables tumor cells to adapt and thrive in harsh microenvironments