title: Emerging metabolic targets in cancer therapy.
abstract: Cancer cells are different from normal cells in their metabolic properties. Normal cells mostly rely on mitochondrial oxidative phosphorylation to produce energy. In contrast, cancer cells depend mostly on glycolysis, the aerobic breakdown of glucose into ATP. This altered energy dependency is known as the "Warburg effect" and is a hallmark of cancer cells. In recent years, investigating the metabolic changes within cancer cells has been a rapidly growing area. Emerging evidence shows that oncogenes that drive the cancer-promoting signals also drive the altered metabolism. Although the exact mechanisms underlying the Warburg effect are unclear, the existing evidence suggests that increased glycolysis plays an important role in support malignant behavior of cancer cells. A thorough understanding of the unique metabolism of cancer cells will help to design of more effective drugs targeting metabolic pathways, which will greatly impact the capacity to effectively treat cancer patients. Here we provide an overview of the current understanding of the Warburg effect upon tumor cell growth and survival, and discussion on the potential metabolic targets for cancer therapy.
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Adam I
authors.initials: AI
authors.lastname: Riker
authors.forename: Oystein
authors.initials: O
authors.lastname: Fodstad
authors.forename: Susan P
authors.initials: SP
authors.lastname: Ledoux
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Wilson
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
mesh_terms: D000263:Adenylate Kinase / Q000037:antagonists & inhibitors; D000970:Antineoplastic Agents / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016259:Genes, myc / Q000187:drug effects; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000037:antagonists & inhibitors; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051793:Hypoxia-Inducible Factor 1; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D006593:Hexokinase; D011770:Pyruvate Kinase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase