On the other hand, hypoxia induces histone hypoacetylation that may be potentially targeted by inhibitors of HDAC.221 Indeed, HDAC inhibitors such as Vorinostat and valproic acid have shown promising results in solid tumors, especially given in combination with chemotherapeutic agents.222, 223, 224, 225 Therefore, approaches to target epigenetic mechanisms should take into consideration of the potential impact of the tumor microenvironment and metabolism. The gene discussed is HDAC9; the disease is neoplasm.