Metabolic shifts in glioblastoma: unraveling altered pathways and exploring novel therapeutic avenues

Abstract

Metabolic reprogramming stands out as a defining characteristic of cancer, including glioblastoma (GB), enabling tumor cells to overcome growth and survival challenges in adverse conditions. The dysregulation of metabolic processes in GB is crucial to its pathogenesis, influencing both tumorigenesis and the disease's invasive tendencies. This altered metabolism supplies essential energy substrates for uncontrolled cell proliferation and also creates an immunosuppressive microenvironment, complicating conventional therapies. A comprehensive understanding of the complexities of metabolic dysregulation in carbohydrate, amino acid, lipid and nucleotide pathways in GB holds promise for effective therapeutic interventions. Key metabolic enzymes, transporters, and signaling pathways and mitochondrial metabolism have been examined for their roles in GB pathology and their possible therapeutic potential. Addressing these metabolic targets has shown efficacy in preclinical models and is currently being evaluated in clinical trials. Combination therapies that exploit metabolic vulnerabilities alongside conventional treatments hold the promise of improving patient outcomes. This review explores the dynamic interplay between glioblastoma's aggressiveness and altered metabolism, offering insights into potential therapeutic strategies. Moreover, this review discusses the recent advancements in drug development aimed at targeting these dysregulated metabolic pathways.

Keywords: Altered metabolism; Carbohydrate metabolism; Combination therapies; Glutamine; Lipid metabolism; Metabolic reprogramming.