Histone deacetylase inhibitors: SAHA (Vorinostat). A treatment option for advanced cutaneous T-cell lymphoma

Introduction Deactylases (DACs) belong to one of three highly conserved classes of 18+ known enzymes whose function is to remove acetyl groups from various proteins. Histone acetylases are enzymes that acetylate proteins and have been found to be mutated in cancer cells. There is a balance between deacetylation and acetylation which controls gene transcription. Although best known for their acetylation of DNA histone proteins, these enzymes predate histones and are responsible for acetylating a large number of other proteins, including tumors suppressors such as p53. Epigenetic variations of DNA are important as signals for gene transcription or silencing. Epigeneic modulation of gene transcription through de-methylation and acetylation. is a novel approach for the treatment of cancer. HDAC inhibitors are small molecule inhibitors of HDACs (Marks 2000). They represent a new class of antitumor agents that can induce a number of important anti-proliferative effects: differentiation, cell cycle growth arrest, or apoptosis in various cancer cell lines (Richon 2006).