Histone deacetylase inhibitors as a potential therapeutic agent for human cancer treatment

Abstract

Recent evidence pointed that remodeling of the chromatin template by inhibition of the enzyme histone deacetylase could be a promising approach for the treatment of human cancer. Alterations in histone acetylation may lead to changes in chromatin structure and transcriptional dysregulation of genes that are implicated in controlling cell cycle progression or pathways regulating cell differentiation and apoptosis. The histone deacetylase (HDAC) inhibitors are currently a new class of antineoplastic agents. They bind DNA tightly to histones, preventing the transcription of several tumor suppression genes without modifying DNA sequence. At present, there are already too many HDAC inhibitors available and hopefully some of them could help substantially in the prevention and treatment of cancer. First clinical studies have shown that histone hyperacetylation can be achieved safely in humans and that treatment of cancer with such agents seems to be becoming possible. Several ongoing National Institute of Health (NIH) trials are investigating the use of these agents in combination with potent chemotherapeutic agents, with the aim of increasing their efficiency. Further studies are needed to delineate the optimal dosage, the duration of therapy and possibly the efficacy of other agents able to synergize with HDAC inhibitors in the fight against cancer.