Clinical Applications of Histone Deacetylase Inhibitors

Aberrations in histone acetyltransferases (HATs) and histone deacetylases (HDACs) have been associated with tumor development and tumor progression. Pharmacological interference with histone acetylation and methylation has shown to be promising for the treatment and prevention of cancer, however, its optimal application remains under investigation. Several structurally and functionally different HDAC inhibitors (HDACi) have been developed to reverse aberrant epigenetic changes in cancer cells. With a growing body of literature, there is ample preclinical rationale to test these drugs in various stages and settings of cancer, either as single agents or in rationally designed combinations as a therapeutic strategy in hematological as well as solid tumor malignancies. The first HDACi vorinostat (Zolinza) was approved for the treatment of patients with cutaneous T-cell lymphoma. HDACi have also demonstrated great promise in treating a variety of noncancer diseases, including epilepsy, cystic fibrosis, spinal muscular atrophy, and human immunodeficiency virus infection.