title: Rewiring the solid tumor epigenome for cancer therapy.
abstract: BACKGROUND
  Whereas tumorigenic processes have traditionally been attributed to gene amplification, deletion, or mutation, it is now clear that epigenetic changes represent an additional hallmark of cancer. This review explains the basic principles of epigenetic regulation and therapy, provides an overview of clinically approved drugs, introduces novel targets and compounds, and discusses the potential reasons behind treatment success and failure.
  
  
  METHODS
  We provide a brief introduction to the concept of epigenetic regulation in general and explain how epigenetic pathways are altered in cancer. Based on this, we go on to explore the rational behind epigenetic cancer therapy, provide an overview of clinical success and failure of specific drugs, describe novel pharmaceutical targets, review epigenetic combination treatment, and finally discuss biological concepts influencing treatment success. Expert commentary: Even though many early epigenetic therapy trials had disappointing results, lessons learned from these studies have heavily influenced the design of modern trials leading to improved therapeutic outcomes. Better preclinical model systems may help to reduce the risk of clinical failure and to identify high-confidence targets for clinical follow-up.
authors.affiliation: a The David H. Koch Institute for Integrative Cancer Research , Cambridge , MA , USA.|b Departments of Biology , Massachusetts Institute of Technology , Cambridge , MA , USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Braun
authors.affiliation: a The David H. Koch Institute for Integrative Cancer Research , Cambridge , MA , USA.|b Departments of Biology , Massachusetts Institute of Technology , Cambridge , MA , USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D015894:Genome, Human; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: Cancer; chromatin; combination treatment; epigenetics; personalized medicine; solid tumors