Valproic acid malignancies for the treatment of myeloid

Valproic acid (VPA) has been used as an anticonvulsant for decades. Recently, it was demonstrated that VPA also acts as a histone deacetylase inhibitor and induces differentiation and apoptosis in a variety of malignant cells in vitro. The effect of VPA on tumor cells differs according to cell type, degree of differentiation, and underlying genetic alterations. Clinical trials with VPA have focused on acute myeloid leukemia and the myelodysplastic syndromes. When it was used as monotherapy or in combination with all-trans retinoic acid, which synergizes in vitro, VPA achieved hematologic improvement in a subset of patients. Similar to other inhibitors of histone deacetylases, complete or partial remissions rarely were observed. In this report, the authors reviewed the in vitro and in vivo data obtained with VPA, and they considered possible combination regimens aimed at improving therapeutic efficacy. Cancer 2007;110:943-54. (c) 2007 American Cancer Society.