Metabolic Landscape and Emerging Therapeutic Potential in Pediatric and Adult Gliomas.
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The underlying metabolism of tumor cells in gliomas has become an area of focus secondary to the difficulties in diagnosis and treatment of these tumors. Heterogeneity in both molecular and phenotypic features of tumor cells in pediatric and adult gliomas presents a significant barrier to traditional treatment options such as radiotherapy and chemotherapy. Low-grade gliomas in pediatric and adult populations have relatively high survival rates, while high-grade gliomas have no effective treatments. Recent advancements in metabolomic techniques have uncovered key metabolic abnormalities, such as increased glutamine and creatinine in invasive edge cells and increased purines in viable tumor cells, distinguishing tumor cells in gliomas. Spatial metabolic heterogeneity and metabolic plasticity enable gliomas to adapt to diverse microenvironments and oxidative stress, necessitating precision medicine approaches that target subtype-specific metabolic vulnerabilities. Further, gliomas are characterized by high intratumoral heterogeneity, with metabolic distinctions between core, edge, viable, and necrotic regions. Altered metabolism of tumor cells has an impact on cells within the tumor microenvironment, resulting in a dysfunctional phenotypic state in resident cells. These metabolic abnormalities differentiate tumor cells from the surrounding microenvironment. Enhanced understanding of the metabolic abnormalities in gliomas could inform targeted therapies, increasing therapeutic response in patients. This review synthesizes emerging evidence on intratumoral and intertumoral heterogeneity in gliomas, highlights the role of tumor-immune cell crosstalk in shaping the metabolic landscape, and discusses how these vulnerabilities may be exploited to develop novel therapies.