Epigenetic targeted anti-cancer drugs: an unfolding story.

摘要

Boumber and Issa provide a useful review of the development of agents that target the epigenome—primarily DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors. The authors provide a summary of agents approved for clinical use: the DNMT inhibitors azacitidine (Vidaza) and decitabine (Dacogen), and the HDAC inhibitors vorinostat (Zolinza) and romidepsin (Istodax). In addition, they summarize available clinical trial data from a number of novel drugs that target the epigenome. As the authors indicate, this list is selective. There are at least another 12 to 15 “epigenetic drugs” in clinical trials, and many more in various stages of preclinical development.[1,2] While Boumber and Issa state that HDAC inhibitors lead to activation of genes, several studies have shown that about the same number of genes are up-regulated as are down-regulated by these epigenetic modifying agents.[3] The mechanism of action of the HDAC inhibitors is not well understood.