Targeting Energy Metabolism to Overcome Therapeutic Resistance of Glioblastoma and Tumor-associated Edema

Glioblastoma remains among the most lethal of human malignancies. The current standard of care prolongs life expectancy about 2 months on average compared to from radiation therapy alone, leading to a median patient survival of 14.6 months. Glioblastoma is heterogenous tumor at various levels, and intrinsically resistance to radiation and chemotherapy. These limits therapeutic options for both primary and recurrent tumors. Importantly, glioblastoma progression is often accompanied by cerebral edema, a significant cause of morbidity that influences the clinical course and prognosis of the disease. Immunosuppressive corticosteroids have been the primary treatment for glioblastoma-associated edema. However, the effect is temporary and accompanied by adverse effects due to the action of corticosteroids outside of the targeted area. Research over the past two decades has unveiled a significant role for metabolic reprogramming that confers a survival advantage during gliomagenesis and therapeutic resistance. This chapter introduces the recent discoveries of two energy metabolism pathways: AMP-activated kinase-mediated stress-resilient glioblastoma growth, and Guanosine-5’-triphosphate (GTP)- metabolic reprogramming that renders anabolic growth and radioresistance. We discuss the potential clinical utility of currently available medicine that could target these metabolic pathways to suppress malignant growth of glioblastoma and increase the efficacy of the current glioblastoma therapy.