title: Targeting metabolic remodeling in glioblastoma multiforme.
abstract: A key aberrant biological difference between tumor cells and normal differentiated cells is altered metabolism, whereby cancer cells acquire a number of stable genetic and epigenetic alterations to retain proliferation, survive under unfavorable microenvironments and invade into surrounding tissues. A classic biochemical adaptation is the metabolic shift to aerobic glycolysis rather than mitochondrial oxidative phosphorylation, regardless of oxygen availability, a phenomenon termed the "Warburg Effect". Aerobic glycolysis, characterized by high glucose uptake, low oxygen consumption and elevated production of lactate, is associated with a survival advantage as well as the generation of substrates such as fatty acids, amino acids and nucleotides necessary in rapidly proliferating cells. This review discusses the role of key metabolic enzymes and their association with aerobic glycolysis in Glioblastoma Multiforme (GBM), an aggressive, highly glycolytic and deadly brain tumor. Targeting key metabolic enzymes involved in modulating the "Warburg Effect" may provide a novel therapeutic approach either singularly or in combination with existing therapies in GBMs.
authors.affiliation: The Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Amparo
authors.initials: A
authors.lastname: Wolf
authors.forename: Sameer
authors.initials: S
authors.lastname: Agnihotri
authors.forename: Abhijit
authors.initials: A
authors.lastname: Guha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004798:Enzymes / Q000378:metabolism; D015894:Genome, Human; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D058990:Molecular Targeted Therapy / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D004798:Enzymes