EZH2 as a potential target in cancer therapy

Epigenomics. 2014 Jun;6(3):341-51. doi: 10.2217/epi.14.23.

Abstract

Over the last several years, dysregulation of epigenetic mechanisms including DNA and histone methylation has been recognized as a hallmark of cancer. Alterations of epigenetic regulators themselves, including the histone lysine methyltransferase EZH2, have been reported in numerous cancer types. With the discovery of small molecule inhibitors of EZH2, we can now begin to evaluate EZH2 as a therapeutic target in cancer. This article will provide an overview of the dysregulation of EZH2 in cancer, possible mechanisms for inhibition of EZH2 activity, and the preclinical activity of currently available EZH2 inhibitors.

Keywords: EZH2; PRC2; cancer; histone lysine methyltransferase; small molecule inhibitor.

Publication types

  • Review

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Enhancer of Zeste Homolog 2 Protein
  • Epigenesis, Genetic
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Polycomb Repressive Complex 2 / antagonists & inhibitors*
  • Polycomb Repressive Complex 2 / chemistry
  • Polycomb Repressive Complex 2 / genetics
  • Small Molecule Libraries / pharmacology*

Substances

  • Small Molecule Libraries
  • 3-deazaneplanocin
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • Adenosine