Role of Histone Methylation in Cancer: Pathobiology and Therapeutics

Abstract

Cancer is among the most common causes of death in the world. Despite the recent breakthroughs over the last few decades, further research studies are required to improve current cancer treatment. In the last decade, the function of dysregulated epigenetic variations in cancer development and progression has become clearer. Epigenetic modifications are mostly reversible, hence suitable for pharmacological interventions in cancer therapy. Lysine methyltransferases and demethylases play a dynamic role in cancer, regulating chromatin architecture and thus gene transcription by methylation of lysine residues on histone proteins. An aberrant rise in histone methylation levels has been linked to cancer spread. Inhibitors of methyltransferases and demethylases have shown anti-cancer activity in a variety of malignancies, and several lead compounds are currently being tested in clinical studies. Here, we summarize the roles of ROS, histone methylation, SET domain containing KMTs and non-SET domain containing KMTs in regulating the pathological processes in cancer, with the goal of providing a new perspective on cancer management by highlighting the recent advances in small molecular inhibitors for cancer treatment. Histone methyltransferase and histone demethylases (KDMs) are majorly found to be upregulated in most cancers. Accumulated evidence and a growing interest in cancer therapy have led to the identification and development of new inhibitors that are capable of blocking the activity of HMTs, thus preventing tumor progression.