HDAC inhibitors: Promising agents for leukemia treatment

Abstract

The essential role of epigenetic modification in the pathogenesis of a series of cancers have gradually been recognized. Histone deacetylase (HDACs), as well-known epigenetic modulators, are responsible for DNA repair, cell proliferation, differentiation, apoptosis and angiogenesis. Studies have shown that aberrant expression of HDACs is found in many cancer types. Thus, inhibition of HDACs has provided a promising therapeutic approach alternative for these patients. Since HDAC inhibitor (HDACi) vorinostat was first approved by the Food and Drug Administration (FDA) for treating cutaneous T-cell lymphoma (CTCL) in 2006, the combination of HDAC inhibitors with other molecules such as chemotherapeutic drugs has drawn much attention in current cancer treatment, especially in hematological malignancies therapy. Up to now, there have been more than twenty HDAC inhibitors investigated in clinic trials with five approvals being achieved. Indeed, Histone deacetylase inhibitors promote or enhance several different anticancer mechanisms and therefore are in evidence as potential antileukemia agents. In this review, we will focus on possible mechanisms by how HDAC inhibitors exert therapeutic benefit and their clinical utility in leukemia.