A work in progress: the clinical development of histone deacetylase inhibitors.

It has been widely recognized that histone deacetylases (HDAC) are promising targets in the field of oncology. An impressive body of preclinical research points to the ability of HDAC inhibitors (HDACIs) to modulate a wide variety of cellular functions, including cell differentiation, cell cycle progression, apoptosis, cytoskeletal modifications and angiogenesis. Originally developed as epigenetic drugs because of their ability to inhibit histones deacetylation, HDACIs are now being considered also because of their effects on other acetylation-regulated proteins with pivotal roles in transformed cells. This review will highlight the clinical development of HDACIs in oncology and will try to discuss the several major open clinical issues challenging the successful clinical development of HDACIs, with a particular emphasis on the spectrum of activity of these agents, the best development strategy in solid tumors, the cardiac side effects and bio-markers to be used in clinical trials.