Targeting EZH2 in cancer

Nat Med. 2016 Feb;22(2):128-34. doi: 10.1038/nm.4036.


Recent genomic studies have resulted in an emerging understanding of the role of chromatin regulators in the development of cancer. EZH2, a histone methyl transferase subunit of a Polycomb repressor complex, is recurrently mutated in several forms of cancer and is highly expressed in numerous others. Notably, both gain-of-function and loss-of-function mutations occur in cancers but are associated with distinct cancer types. Here we review the spectrum of EZH2-associated mutations, discuss the mechanisms underlying EZH2 function, and synthesize a unifying perspective that the promotion of cancer arises from disruption of the role of EZH2 as a master regulator of transcription. We further discuss EZH2 inhibitors that are now showing early signs of promise in clinical trials and also additional strategies to combat roles of EZH2 in cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Benzamides / therapeutic use
  • Biphenyl Compounds
  • Drug Resistance, Neoplasm
  • Enhancer of Zeste Homolog 2 Protein
  • Humans
  • Indazoles / therapeutic use
  • Indoles / therapeutic use
  • Molecular Targeted Therapy
  • Morpholines
  • Mutation*
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Polycomb Repressive Complex 2 / antagonists & inhibitors
  • Polycomb Repressive Complex 2 / genetics*
  • Polycomb-Group Proteins / antagonists & inhibitors
  • Polycomb-Group Proteins / genetics
  • Pyridones / therapeutic use


  • Benzamides
  • Biphenyl Compounds
  • EPZ005687
  • GSK-2816126
  • GSK343
  • Indazoles
  • Indoles
  • Morpholines
  • Polycomb-Group Proteins
  • Pyridones
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • tazemetostat