not received Plenary IV. Mitochondria and cancer Metabolic Management of Glioblastoma Thomas Seyfried Department of Biology, Boston College, Chestnut Hill, Massachusetts, United States Glioblastoma multiforme (GBM) remains among the most aggressive and difficult to manage primary brain tumours in humans. Glucose and glutamine are recognized as the major fuels that drive GBM growth and invasion through glycolysis and glutaminolysis, respectively. The glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), was administered together with a calorically restricted ketogenic diet (KD-R) to treat late-stage orthotopic growth in two syngeneic mouse models of GBM; the highly invasive mesenchymal tumour, VM-M3, and the high-grade stem cell glioma, CT-2A. DON targets glutaminolysis while the KD-R reduces glucose and, at the same time, elevates neuroprotective and non-fermentable ketone bodies. The diet/drug therapeutic strategy caused massive tumour cell death or mitotic arrest, while reversing disease symptoms and improving overall survival without toxicity. The therapeutic strategy also reduced edema, hemorrhage, and inflammation associated with rapid tumour growth. Moreover, the KD-R diet facilitated DON delivery to the brain and allowed a lower nontoxic dosage to achieve therapeutic effect. Data from human case reports will also be presented. These findings support the importance of glucose and glutamine in driving GBM growth and provide a plausible therapeutic strategy for the non-toxic metabolic management of GBM.
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