Crosstalk of Epigenetic and Metabolic Signaling Underpinning Glioblastoma Pathogenesis

SIMPLE SUMMARY: Epigenetic mechanisms can modulate key genes involved in the cellular metabolism of glioblastomas and participate in their pathogenesis by increasing their heterogeneity, plasticity, and malignancy. Although most epigenetic modifications can primarily promote the activity of metabolic pathways, they may also exert an inhibitory role. The detection of key metabolic alterations in gliomas regulated by epigenetic mechanisms will enable drug development and effective molecular targeting, improvement of therapeutic schemes, and patients’ management. ABSTRACT: Metabolic alterations in neoplastic cells have recently gained increasing attention as a main topic of research, playing a crucial regulatory role in the development and progression of tumors. The interplay between epigenetic modifications and metabolic pathways in glioblastoma cells has emerged as a key pathogenic area with great potential for targeted therapy. Epigenetic mechanisms have been demonstrated to affect main metabolic pathways, such as glycolysis, pentose phosphate pathway, gluconeogenesis, oxidative phosphorylation, TCA cycle, lipid, and glutamine metabolism by modifying key regulatory genes. Although epigenetic modifications can primarily promote the activity of metabolic pathways, they may also exert an inhibitory role. In this way, they participate in a complex network of interactions that regulate the metabolic behavior of malignant cells, increasing their heterogeneity and plasticity. Herein, we discuss the main epigenetic mechanisms that regulate the metabolic pathways in glioblastoma cells and highlight their targeting potential against tumor progression.