Histone Methyltransferase Inhibitors for Cancer Therapy

Epigenetics is the study of heritable changes in gene expression without alterations in the underlying DNA sequence. Efforts have been made to understand aspects of epigenetic regulation in normal and cancer cells. With the recent discoveries of key histone methyltransferases, it is an exciting time for the field of epigenetics, particularly for enzymes that have been shown to be the writers of epigenetic markers on genes coding for proteins in cancer. Thus, the development of highly potent and specific small-molecule inhibitors to cancer-related histone methyltransferases shows great promise as a therapeutic option. In this review, we focus on the cancer-related histone methyltransferases, including lysine methyltransferases such as DOT1L, EZH2, G9a, and MLL, as well as arginine methyltransferases. We summarize the enzyme characters, their relations to different cancers, and the drug discoveries targeted to these key enzymes.