Targeting histone methylation for colorectal cancer

Tao Huang, Chengyuan Lin, Lidan Zhong, Ling Zhao, Ge Zhang, Aiping Lyu, Jiang Wu, Zhaoxiang Bian*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

38 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)114-131
Number of pages18
JournalTherapeutic Advances in Gastroenterology
Issue number1
Publication statusPublished - 1 Jan 2017

Scopus Subject Areas

  • Gastroenterology

User-Defined Keywords

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


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