Epigenetic-based therapies in cancer: progress to date

Drugs. 2011 Dec 24;71(18):2391-403. doi: 10.2165/11596690-000000000-00000.

Abstract

Epigenetic gene silencing is a hallmark of cancer cells. Two important types of epigenetic changes are DNA methylation and histone modification. These modifications are catalysed by DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), resulting in chromatin structure changes and gene inactivation. Interestingly, inhibition of these enzymes is known to induce differentiation or apoptosis of cancer cells. Therefore, DNMTs and HDACs have become attractive therapeutic targets. In recent years, many different DNMT and HDAC inhibitors have been developed, and multiple molecular mechanisms through which these agents exert anti-cancer effects have been identified. While a large number of clinical trials are ongoing, hypomethylating agents and HDAC inhibitors seem to be promising for treating several types of cancer. Moreover, developing effective strategies of combining epigenetic therapy with conventional chemotherapy will be one of the major challenges in the future. We briefly review current advances in epigenetic therapies with a focus on recently reported clinical trials.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use*
  • DNA Methylation / genetics
  • DNA Modification Methylases / chemistry
  • DNA Modification Methylases / genetics
  • DNA Modification Methylases / therapeutic use*
  • Epigenesis, Genetic / drug effects*
  • Gene Silencing*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Deacetylase Inhibitors / therapeutic use*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / genetics

Substances

  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • DNA Modification Methylases