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Therap Adv Gastroenterol. 2017 Jan;10(1):114-131. doi: 10.1177/1756283X16671287. Epub 2016 Oct 25.

Targeting histone methylation for colorectal cancer.

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Lab of Brain-Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, PR China.
Lab of Brain-Gut Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, PR China YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming, PR China.
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, PR China.
Room 307, Jockey Club School of Chinese Medicine Building, 7 Hong Kong Baptist University Road, Kowloon Town, Kowloon, Hong Kong.


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.


colorectal cancer; drug targets; epigenetic regulation; histone demethylase; histone methyltransferase

Conflict of interest statement

Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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