Introduction
Glioblastoma (GBM) is an aggressive primary human brain tumour that has resisted effectiveGlioblastoma (GBM) is an aggressive primary human brain tumour that has resisted effectivetherapy for decades. Although glucose and glutamine are the major fuels that drive GBMgrowth and invasion, few studies have targeted these fuels for therapeutic management. Theglutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), was administered together with acalorically restricted ketogenic diet (KD-R) to treat late-stage orthotopic growth in twosyngeneic GBM mouse models: VM-M3 and CT-2A. DON targets glutaminolysis, while theKD-R reduces glucose and, simultaneously, elevates neuroprotective and non-fermentableketone bodies. The diet/drug therapeutic strategy killed tumour cells while reversing diseasesymptoms, and improving overall mouse survival.