title: EZH2 as a potential target in cancer therapy.
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.
authors.affiliation: Cancer Epigenetics Discovery Performance Unit, Oncology R&D, GlaxoSmithKline, 1250 S. Collegeville Road, Collegeville, PA 19426, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McCabe
authors.forename: Caretha L
authors.initials: CL
authors.lastname: Creasy
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D054852:Small Molecule Libraries; C048460:3-deazaneplanocin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D000241:Adenosine
keywords: EZH2; PRC2; cancer; histone lysine methyltransferase; small molecule inhibitor