title: Molecular Pathways: Targeting MYC-induced metabolic reprogramming and oncogenic stress in cancer.
abstract: MYC is a multifunctional transcription factor that is deregulated in many human cancers. MYC impacts a collaborative genetic program that orchestrates cell proliferation, metabolism, and stress responses. Although the progression of MYC-amplified tumors shows robust dependence on MYC activity, directly targeting MYC as a therapeutic method has proven to be technically difficult. Therefore, alternative approaches are currently under development with a focus on interference with MYC-mediated downstream effects. To fuel rapid cell growth, MYC reprograms cancer cell metabolism in a way that is substantially different from normal cells. The MYC-induced metabolic signature is characterized by enhanced glucose and glutamine uptake, increased lactate production, and altered amino acid metabolism. Targeting MYC-reprogrammed cancer cell metabolism is considered to be promising based on multiple preclinical studies. In addition, the increased biosynthetic demand of MYC-driven tumors coupled with limited nutrient access within tumor microenvironments create multiple levels of oncogenic stress, which can also be used as tumor-specific targets for pharmacologic intervention. Presumably, the best therapeutic strategy for treating MYC-amplified tumors is combined targeting of multiple MYC-mediated pathways, especially those involved in regulating cell proliferation, metabolism, and oncogenic stress.
authors.affiliation: Authors' Affiliations: Abramson Family Cancer Research Institute, Perelman School of Medicine at the University of Pennsylvania; and Howard Hughes Medical Institute, Philadelphia, Pennsylvania.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: M Celeste
authors.initials: MC
authors.lastname: Simon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological; D057170:Translational Research, Biomedical
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D016271:Proto-Oncogene Proteins c-myc
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