Trials with ‘epigenetic’ drugs: An update

Epigenetic inactivation of pivotal genes involved in correct cell growth is a hallmark of human pathologies, in particular cancer. These epigenetic mechanisms, including crosstalk between DNA methylation, histone modifications and non-coding RNAs, affect gene expression and are associated with disease progression. In contrast to genetic mutations, epigenetic changes are potentially reversible. Re-expression of genes epigenetically inactivated can result in the suppression of disease state or sensitization to specific therapies. Small molecules that reverse epigenetic inactivation, so-called epi-drugs, are now undergoing clinical trials. Accordingly, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for cancer treatment have approved some of these drugs. Here, we focus on the biological features of epigenetic molecules, analyzing the mechanism(s) of action and their current use in clinical practice.

► Epi-drugs play a key role in pathogenesis and tumorigenesis. ► Epi-drugs in clinical trials provide exciting results in human diseases therapy. ► Epi-drugs may provide an opportunity to develop tailor-made therapies. ► Epi-drugs enhance the effects of combination therapy. ► Epi-drugs increase sensitivity to classical anti-cancer agents.