Targeting epigenetic regulators for cancer therapy: modulation of bromodomain proteins, methyltransferases, demethylases, and microRNAs.

INTRODUCTION: Histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) were the first epigenetic targets to be successfully addressed for cancer treatment, but more recently additional families of epigenetic modulators have been the subject of intense research. Potent inhibitors have been identified in several instances and have proven to be invaluable tools for studying these proteins in normal physiology and in disease. Some have now progressed to clinical studies in hematological and solid tumors, and encouraging early results have been reported.

AREAS COVERED: This article reviews recent advances regarding the roles of new epigenetic players beyond HDACs and DNMTs in cancer, and discusses the impact of selective chemical probes on unravelling their function. The emerging field of non-coding RNAs (ncRNAs) and ongoing clinical studies with epigenetic drugs and microRNAs (miRNAs) are also addressed.

EXPERT OPINION: The roles of different epigenetic factors in numerous cancers have been unraveled recently, leading to the initiation of clinical studies. With inhibitors of BET bromodomain proteins, the histone methyltransferases EZH2 and DOT1L, and the histone demethylase LSD1 progressing through clinical trials, and the recognition of the importance of ncRNAs as potential biomarkers and therapeutics, this bears the hope that novel epigenetic therapies will be approved soon.