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

Targeting EZH2 in cancer.

Kim KH1,2,3,4, Roberts CW1,2,3,4,5.

Author information

1
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
2
Division of Hematology/Oncology, Boston Children's Hospital, Massachusetts, USA.
3
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
4
Broad Institute of Harvard and Massachusetts Institute of Technology, Boston, Massachusetts, USA.
5
Comprehensive Cancer Center and Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.

Abstract

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.

PMID:
26845405
PMCID:
PMC4918227
DOI:
10.1038/nm.4036
[Indexed for MEDLINE]
Free PMC Article

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