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9. Metabolic management of glioblastoma

Thomas Nicholas Seyfried

Department of Biology, Boston College, Chestnut Hill, MA 02467, USA.

Glioblastoma multiforme (GBM) remains among the most aggressive and difficult to manage primary
brain tumors in humans. Abnormalities in the number, structure, and function of GBM mitochondria
compromise energy metabolism through OxPhos. Glucose and glutamine are recognized as the major
fermentable fuels that drive GBM growth 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 tumor, VM-M3, and the high-grade stem cell glioma, CT-2A. DON targets
glutaminolysis while KD-R reduces glucose and, at the same time, elevates neuroprotective and non-
fermentable ketone bodies. The diet/drug therapeutic strategy caused massive tumor 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 tumor 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 are also 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 and any cancer with mitochondrial defects.

10. Novel perspectives on the immune environment of acute myeloid leukemia using
multiomyx

Josette William, Nicholas Hoe, Mate Nagy, Raghav Padmanabhan, Qingyan Au

NeoGenomics, Aliso Viejo, CA 92656, USA.

Background and aim: Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disorder.
Despite its poor prognosis, the treatment of AML remains largely unchanged over the past several decades
with high-dose chemotherapy remaining the mainstay of therapy. This has led to interest in exploring novel
therapeutic approaches, such as bispecific antibodies, chimeric antigen receptor T cells, tumor vaccines,
and immune checkpoint inhibitors.