title: Taking on challenging targets: making MYC druggable.
abstract: The transcription factor proto-oncogene c-MYC (hereafter MYC) was first identified more than 3 decades ago and has since been found deregulated in a wide variety of the most aggressive human malignancies. As a pleiotropic transcription factor, MYC directly or indirectly controls expression of hundreds of coding and noncoding genes, which affect cell cycle entry, proliferation, differentiation, metabolism, and death/survival decisions of normal and cancer cells. Tumors with elevated MYC expression often exhibit highly proliferative, aggressive phenotypes, and elevated MYC expression has been correlated with diminished disease-free survival for a variety of human cancers. The use of MYC overexpression or MYC-dependent transcriptional gene signatures as clinical biomarkers is currently being investigated. Furthermore, preclinical animal and cell-based model systems have been extensively utilized in an effort to uncover the mechanisms of MYC-dependent tumorigenesis and tumor maintenance. Despite our ever-growing understanding of MYC biology, currently no targeted therapeutic strategy is clinically available to treat tumors that have acquired elevated MYC expression. This article summarizes the progresses being made to discover and implement new therapies to kill MYC over-expressing tumors-a target that was once deemed undruggable.
authors.affiliation: From the Department of Cell & Tissue Biology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; the Department of Cell & Tissue Biology and Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA; and the Department of Cell & Tissue Biology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Dai
authors.initials: D
authors.lastname: Horiuchi
authors.affiliation: From the Department of Cell & Tissue Biology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; the Department of Cell & Tissue Biology and Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA; and the Department of Cell & Tissue Biology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Anderton
authors.affiliation: From the Department of Cell & Tissue Biology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA; the Department of Cell & Tissue Biology and Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA; and the Department of Cell & Tissue Biology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
authors.forename: Andrei
authors.initials: A
authors.lastname: Goga
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc