title: Exploiting the Epigenome to Control Cancer-Promoting Gene-Expression Programs.
abstract: The epigenome is a key determinant of transcriptional output. Perturbations within the epigenome are thought to be a key feature of many, perhaps all cancers, and it is now clear that epigenetic changes are instrumental in cancer development. The inherent reversibility of these changes makes them attractive targets for therapeutic manipulation, and a number of small molecules targeting chromatin-based mechanisms are currently in clinical trials. In this perspective we discuss how understanding the cancer epigenome is providing insights into disease pathogenesis and informing drug development. We also highlight additional opportunities to further unlock the therapeutic potential within the cancer epigenome.
authors.affiliation: The Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Gerard L
authors.initials: GL
authors.lastname: Brien
authors.affiliation: The Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Daria G
authors.initials: DG
authors.lastname: Valerio
authors.affiliation: The Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: armstros@mskcc.org.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Armstrong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002843:Chromatin / Q000187:drug effects / Q000235:genetics; D002869:Chromosome Aberrations; D002986:Clinical Trials as Topic; D019175:DNA Methylation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D057890:Epigenomics; D015972:Gene Expression Regulation, Neoplastic; D042421:Histone Code / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D058990:Molecular Targeted Therapy; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000517:prevention & control / Q000628:therapy; D015513:Oncogene Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D035703:Therapies, Investigational; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D004273:DNA, Neoplasm; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009363:Neoplasm Proteins; D015513:Oncogene Proteins
keywords: Cancer; chromatin; epigenome; histone modification; targeted therapy