Histone deacetylase inhibitors: biology and mechanism of action.
Histone deacetylases (HDACs) and histone acetyltransferases are enzymes that regulate chromatin structure and function through the removal and addition, respectively, of the acetyl group from the lysine residues of core nucleosomal histones. This posttranslational modification of histones is an important process in the regulation of gene expression. Aberrant expression and recruitment and disrupted activities of HDACs and histone acetyltransferases have been found in malignant tissues, implicating their involvement in cancer. HDAC inhibitors (HDACIs) function through diverse mechanisms, including the promotion of cell cycle arrest and apoptosis and the inhibition of angiogenesis. Malignant cells appear more sensitive to the proapoptotic effects of HDACIs, underscoring the therapeutic potential of these agents. Multiple HDACIs are currently under investigation in clinical trials, including vorinostat (suberoylanilide hydroxamic acid), which was recently approved by the U.S. Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients with progressive, persistent, or recurrent disease on or after 2 systemic therapies.
Mehnert
Janice M
JM
Department of Medical Oncology, Yale Cancer Center, New Haven, CT 06520-8032, USA.
Kelly
Wm Kevin
WK
D020533:Angiogenesis Inhibitors / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000503:physiopathology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases