The metabolomic landscape plays a critical role in glioma oncogenesis

• Published in: Cancer science Vol. 113; no. 5; pp. 1555 - 1563
• Main Authors: Masui, Kenta, Cavenee, Webster K., Mischel, Paul S., Shibata, Noriyuki
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2022; John Wiley and Sons Inc
• Subjects: Amino acids; Biomarkers; Brain cancer; Brain tumors; Cancer; Dehydrogenases; Enzymes; Epigenetics; Gene amplification; Genotype & phenotype; Genotypes; Glioblastoma; Glioma cells; Glucose; Growth factors; Intermediates; Kinases; Metabolism; Metabolites; metabolome; Metabolomics; Microenvironments; mTOR complex; Mutation; Nutrient uptake; Nutrients; omics; Peptides; Phenotypes; Phosphorylation; Protein biosynthesis; Proteins; Proteomics; Review; RNA polymerase; Signal transduction; Stem cells; Transcription factors; Tumorigenesis; mTOR complex; glioblastoma; omics; epigenetics; metabolome
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15325

Cancer cells depend on metabolic reprogramming for survival, undergoing profound shifts in nutrient sensing, nutrient uptake and flux through anabolic pathways, in order to drive nucleotide, lipid, and protein synthesis and provide key intermediates needed for those pathways. Although metabolic enzymes themselves can be mutated, including to generate oncometabolites, this is a relatively rare event in cancer. Usually, gene amplification, overexpression, and/or downstream signal transduction upregulate rate‐limiting metabolic enzymes and limit feedback loops, to drive persistent tumor growth. Recent molecular‐genetic advances have revealed discrete links between oncogenotypes and the resultant metabolic phenotypes. However, more comprehensive approaches are needed to unravel the dynamic spatio‐temporal regulatory map of enzymes and metabolites that enable cancer cells to adapt to their microenvironment to maximize tumor growth. Proteomic and metabolomic analyses are powerful tools for analyzing a repertoire of metabolic enzymes as well as intermediary metabolites, and in conjunction with other omics approaches could provide critical information in this regard. Here, we provide an overview of cancer metabolism, especially from an omics perspective and with a particular focus on the genomically well characterized malignant brain tumor, glioblastoma. We further discuss how metabolomics could be leveraged to improve the management of patients, by linking cancer cell genotype, epigenotype, and phenotype through metabolic reprogramming. Cancer cells depend on metabolic reprogramming for survival, undergoing profound shifts in nutrient sensing, nutrient uptake, and flux through anabolic pathways to drive nucleotide, lipid, and protein synthesis, and to provide key intermediates needed for those pathways. Here, we provide an overview of cancer metabolism, especially from an omics perspective and with a particular focus on the genomically well characterized malignant brain tumor, glioblastoma. We further discuss how metabolomics could be leveraged to improve the management of patients, by linking cancer cell genotype, epigenotype, and phenotype through metabolic reprogramming.