Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets

Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumor characterized by rapid growth and a poor prognosis for patients. Despite advancements in treatment, the median survival time for GBM patients remains low. One of the crucial challenges in understanding and treating GBMs involves its remarkable cellular heterogeneity and adaptability. Central to the survival and proliferation of GBM cells is their ability to undergo metabolic reprogramming. Metabolic reprogramming is a process that allows cancer cells to alter their metabolism to meet the increased demands of rapid growth and to survive in the often oxygen- and nutrient-deficient tumor microenvironment. These changes in metabolism include the Warburg effect, alterations in several key metabolic pathways including glutamine metabolism, fatty acid synthesis, and the tricarboxylic acid (TCA) cycle, increased uptake and utilization of glutamine, and more. Despite the complexity and adaptability of GBM metabolism, a deeper understanding of its metabolic reprogramming offers hope for developing more effective therapeutic interventions against GBMs.