Histone deacetylase inhibitors: an overview of the clinical studies in solid tumors

The histone deacetylase inhibitors (HDACi) are a group of small molecules that target histone deacetylases (HDACs) by inhibiting their activity. HDACi have a long history of use in neurology and psychiatry as antiepileptics and mood stabilizers. More recently, they have been investigated as possible treatments for cancer. HDACi have undergone rapid clinical development in recent years, on the basis of their preclinical in-vitro and in-vivo antitumor activity in hematological malignancies and solid tumors. Many HDACi have entered phase I-III clinical trials. Among the HDACi, vorinostat and romidepsin are currently the most extensively studied. In 2006 and 2009, respectively, they received approval by the United States Food and Drug Administration for treatment of cutaneous T-cell lymphoma and romidepsin for the treatment of peripheral T-cell lymphoma. Other HDACi, such as panobinostat and valproic acid, also demonstrated activity as therapeutic anticancer agents. In this article we give an overview of the clinical studies of HDACi in solid tumors. We start with a short description of the working mechanism of HDACi in general.