Targeting EZH2 in cancer

被引：1174

作者：

Kim, Kimberly H. ^{[1
,2
,3
,4
,5
]}

Roberts, Charles W. M. ^{[1
,2
,3
,4
,5
,6
,7
]}

机构：

[1] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

[2] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA

[3] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA

[4] Broad Inst Harvard, Boston, MA USA

[5] MIT, Boston, MA USA

[6] St Jude Childrens Res Hosp, Ctr Comprehens Canc, 332 N Lauderdale St, Memphis, TN 38105 USA

[7] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA

来源：

NATURE MEDICINE | 2016年 / 22卷 / 02期

关键词：

POLYCOMB-REPRESSIVE COMPLEX; HISTONE METHYLTRANSFERASE EZH2; GROUP PROTEIN EZH2; EMBRYONIC STEM-CELLS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHROMATIN REMODELING GENES; NERVE SHEATH TUMORS; SOMATIC MUTATIONS; PROSTATE-CANCER; BREAST-CANCER;

D O I：

10.1038/nm.4036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：128 / 134

页数：7

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