期刊
PHARMACOLOGY & THERAPEUTICS
卷 199, 期 -, 页码 129-138出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pharmthera.2019.02.014
关键词
Super-enhancers; Cancer; Genetic variants; 3D chromatin architecture; Enhancer hijacking; Transcriptional inhibitors
资金
- AACR-Incyte Leukemia Research fellowship
Cancer is fueled by the aberrant activity of oncogenic and tumor suppressive pathways. Transcriptional dysregulation of these pathways play a major role both in the genesis and development of cancer. Dysregulation of transcriptional programs can be mediated by genetic and epigenetic alterations targeting both protein coding genes and non-coding regulatory elements like enhancers and super-enhancers. Super-enhancers, characterized as large clusters of enhancers in close proximity, have been identified as essential oncogenic drivers required for the maintenance of cancer cell identity. As a result, cancer cells are often addicted to the super-enhancer driven transcriptional programs. Furthermore, pharmacological inhibitors targeting key components of super-enhancer assembly and activation have shown great promise in reducing tumor growth and proliferation in several pre-clinical tumor models. This article reviews the current understanding of super-enhancer assembly and activation, the different mechanisms by which cancer cells acquire oncogenic super-enhancers and, finally, the potential of targeting super-enhancers as future therapeutics. (C) 2019 Elsevier Inc. All rights reserved.
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