title: MYC, Metabolism, and Cancer.
abstract: The MYC oncogene encodes a transcription factor, MYC, whose broad effects make its precise oncogenic role enigmatically elusive. The evidence to date suggests that MYC triggers selective gene expression amplification to promote cell growth and proliferation. Through its targets, MYC coordinates nutrient acquisition to produce ATP and key cellular building blocks that increase cell mass and trigger DNA replication and cell division. In cancer, genetic and epigenetic derangements silence checkpoints and unleash MYC's cell growth- and proliferation-promoting metabolic activities. Unbridled growth in response to deregulated MYC expression creates dependence on MYC-driven metabolic pathways, such that reliance on specific metabolic enzymes provides novel targets for cancer therapy.
  
  
  CONCLUSIONS
  MYC's expression and activity are tightly regulated in normal cells by multiple mechanisms, including a dependence upon growth factor stimulation and replete nutrient status. In cancer, genetic deregulation of MYC expression and loss of checkpoint components, such as TP53, permit MYC to drive malignant transformation. However, because of the reliance of MYC-driven cancers on specific metabolic pathways, synthetic lethal interactions between MYC overexpression and specific enzyme inhibitors provide novel cancer therapeutic opportunities.
authors.affiliation: Abramson Family Cancer Research Institute, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Zachary E
authors.initials: ZE
authors.lastname: Stine
authors.affiliation: Abramson Family Cancer Research Institute, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Zandra E
authors.initials: ZE
authors.lastname: Walton
authors.affiliation: Abramson Family Cancer Research Institute, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Altman
authors.affiliation: Abramson Family Cancer Research Institute, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Annie L
authors.initials: AL
authors.lastname: Hsieh
authors.affiliation: Abramson Family Cancer Research Institute, Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania. dangvchi@upenn.edu.
authors.forename: Chi V
authors.initials: CV
authors.lastname: Dang
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D051793:Hypoxia-Inducible Factor 1; D016271:Proto-Oncogene Proteins c-myc