Targeting the histone orthography of cancer: drugs for writers, erasers and readers

Br J Pharmacol. 2015 Jun;172(11):2716-32. doi: 10.1111/bph.12844. Epub 2014 Sep 5.


Gene expression is dynamically controlled by epigenetics through post-translational modifications of histones, chromatin-associated proteins and DNA itself. All these elements are required for the maintenance of chromatin structure and cell identity in the context of a normal cellular phenotype. Disruption of epigenetic regulation is a common event in human cancer. Here, we review the key protein families that control epigenetic signalling through writing, erasing or reading specific post-translational modifications. By exploiting the leading role of epigenetics in tumour development and the reversibility of epigenetic modifications, promising novel epigenetic-based therapies are being developed. In this article, we highlight the emerging low MW inhibitors targeting each class of chromatin-associated protein, their current use in preclinical and clinical trials and the likelihood of their being approved in the near future.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Epigenesis, Genetic / drug effects*
  • Histone Acetyltransferases / antagonists & inhibitors*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylase Inhibitors / therapeutic use
  • Histone Demethylases / antagonists & inhibitors*
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
  • Histones / drug effects*
  • Histones / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Protein Processing, Post-Translational / drug effects*


  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Histones
  • Histone Demethylases
  • Histone-Lysine N-Methyltransferase
  • Histone Acetyltransferases