title: MYC, Metabolic Synthetic Lethality, and Cancer.
abstract: The MYC oncogene plays a pivotal role in the development and progression of human cancers. It encodes a transcription factor that has broad reaching effects on many cellular functions, most importantly in driving cell growth through regulation of genes involved in ribosome biogenesis, metabolism, and cell cycle. Upon binding DNA with its partner MAX, MYC recruits factors that release paused RNA polymerases to drive transcription and amplify gene expression. At physiologic levels of MYC, occupancy of high-affinity DNA-binding sites drives 'house-keeping' metabolic genes and those involved in ribosome and mitochondrial biogenesis for biomass accumulation. At high oncogenic levels of MYC, invasion of low-affinity sites and enhancer sequences alter the transcriptome and cause metabolic imbalances, which activates stress response and checkpoints such as p53. Loss of checkpoints unleashes MYC's full oncogenic potential to couple metabolism with neoplastic cell growth and division. Cells that overexpress MYC, however, are vulnerable to metabolic perturbations that provide potential new avenues for cancer therapy.
authors.affiliation: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Annie L
authors.initials: AL
authors.lastname: Hsieh
authors.affiliation: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. dangvchi@exchange.upenn.edu.|Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. dangvchi@exchange.upenn.edu.|Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. dangvchi@exchange.upenn.edu.
authors.forename: Chi V
authors.initials: CV
authors.lastname: Dang
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D000072020:Synthetic Lethal Mutations / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics
chemical_list: D016271:Proto-Oncogene Proteins c-myc
keywords: Cancer therapy; Glucose; Glutamine; MYC oncogene; Metabolism; Ribosome biogenesis