Trials with 'epigenetic' drugs: an update

Mol Oncol. 2012 Dec;6(6):657-82. doi: 10.1016/j.molonc.2012.09.004. Epub 2012 Oct 6.

Abstract

Epigenetic inactivation of pivotal genes involved in correct cell growth is a hallmark of human pathologies, in particular cancer. These epigenetic mechanisms, including crosstalk between DNA methylation, histone modifications and non-coding RNAs, affect gene expression and are associated with disease progression. In contrast to genetic mutations, epigenetic changes are potentially reversible. Re-expression of genes epigenetically inactivated can result in the suppression of disease state or sensitization to specific therapies. Small molecules that reverse epigenetic inactivation, so-called epi-drugs, are now undergoing clinical trials. Accordingly, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for cancer treatment have approved some of these drugs. Here, we focus on the biological features of epigenetic molecules, analyzing the mechanism(s) of action and their current use in clinical practice.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Chromatin / genetics
  • Chromatin / metabolism
  • Clinical Trials as Topic
  • DNA Modification Methylases / antagonists & inhibitors
  • Epigenesis, Genetic / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Sirtuins / chemistry
  • Sirtuins / pharmacology
  • Sirtuins / therapeutic use

Substances

  • Antineoplastic Agents
  • Chromatin
  • Histone Deacetylase Inhibitors
  • Histones
  • RNA, Untranslated
  • DNA Modification Methylases
  • Sirtuins