Histone Lysine Demethylases as Targets for Anticancer Therapy

Nat Rev Drug Discov. 2013 Dec;12(12):917-30. doi: 10.1038/nrd4154. Epub 2013 Nov 15.


It has recently been demonstrated that the genes controlling the epigenetic programmes that are required for maintaining chromatin structure and cell identity include genes that drive human cancer. This observation has led to an increased awareness of chromatin-associated proteins as potentially interesting drug targets. The successful introduction of DNA methylation and histone deacetylase (HDAC) inhibitors for the treatment of specific subtypes of cancer has paved the way for the use of epigenetic therapy. Here, we highlight key biological findings demonstrating the roles of members of the histone lysine demethylase class of enzymes in the development of cancers, discuss the potential and challenges of therapeutically targeting them, and highlight emerging small-molecule inhibitors of these enzymes.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Drug Delivery Systems / methods*
  • Histone Deacetylase Inhibitors / administration & dosage*
  • Histone Deacetylase Inhibitors / chemistry
  • Histone Demethylases / antagonists & inhibitors*
  • Histone Demethylases / chemistry
  • Histone Demethylases / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology


  • Antineoplastic Agents
  • Histone Deacetylase Inhibitors
  • Histone Demethylases