Targeting histone methylation for colorectal cancer

As a leading cause of cancer deaths worldwide, colorectal cancer (CRC) results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in CRC, particularly aberrant histone methylation mediated by histone methyltransferases (HMTs) and demethylases (HDMs), ha...

Full description

Saved in:
Bibliographic Details
Published in:Therapeutic Advances in Gastroenterology 2017-01, Vol.10 (1), p.114-131
Main Authors: Huang, Tao, Lin, Chengyuan, Zhong, Linda L. D., Zhao, Ling, Zhang, Ge, Lu, Aiping, Wu, Jiang, Bian, Zhaoxiang
Format: Article
Language:English
Subjects:
Colorectal cancer
Enzymes
Epigenetics
Gastroenterology
Reviews
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:As a leading cause of cancer deaths worldwide, colorectal cancer (CRC) results from accumulation of both genetic and epigenetic alterations. Disruption of epigenetic regulation in CRC, particularly aberrant histone methylation mediated by histone methyltransferases (HMTs) and demethylases (HDMs), have drawn increasing interest in recent years. In this paper, we aim to review the roles of histone methylation and associated enzymes in the pathogenesis of CRC, and the development of small-molecule modulators to regulate histone methylation for treating CRC. Multiple levels of evidence suggest that aberrant histone methylations play important roles in CRC. More than 20 histone-methylation enzymes are found to be clinically relevant to CRC, including 17 oncoproteins and 8 tumor suppressors. Inhibitors of EZH2 and DOT1L have demonstrated promising therapeutic effects in preclinical CRC treatment. Potent and selective chemical probes of histone-methylation enzymes are required for validation of their functional roles in carcinogenesis and clinical translations as CRC therapies. With EZH2 inhibitor EPZ-6438 entering into phase I/II trials for advanced solid tumors, histone methylation is emerging as a promising target for CRC.
ISSN:1756-2848
1756-283X
1756-2848
DOI:10.1177/1756283X16671287