Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy

Clin Epigenetics. 2016 May 24:8:57. doi: 10.1186/s13148-016-0223-4. eCollection 2016.

Abstract

The term epigenetics is defined as heritable changes in gene expression that are not due to alterations of the DNA sequence. In the last years, it has become more and more evident that dysregulated epigenetic regulatory processes have a central role in cancer onset and progression. In contrast to DNA mutations, epigenetic modifications are reversible and, hence, suitable for pharmacological interventions. Reversible histone methylation is an important process within epigenetic regulation, and the investigation of its role in cancer has led to the identification of lysine methyltransferases and demethylases as promising targets for new anticancer drugs. In this review, we describe those enzymes and their inhibitors that have already reached the first stages of clinical trials in cancer therapy, namely the histone methyltransferases DOT1L and EZH2 as well as the demethylase LSD1.

Keywords: Clinical trial; Demethylase inhibitors; Epigenetics; Histone demethylase; Histone methyltransferase; Histone modifications; Lysine methylation; Methylome; Methyltransferase inhibitors.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic / drug effects
  • Histone Demethylases / antagonists & inhibitors*
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
  • Humans
  • Methyltransferases / antagonists & inhibitors
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Histone Demethylases
  • KDM1A protein, human
  • DOT1L protein, human
  • Histone Methyltransferases
  • Methyltransferases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase