Valproic acid for the treatment of myeloid malignancies.
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.
Kuendgen
Andrea
A
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Duesseldorf, Germany. kuendgen@med.uni-duesseldorf.de
Gattermann
Norbert
N
D000208:Acute Disease; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use
D056572:Histone Deacetylase Inhibitors; D014212:Tretinoin; D014635:Valproic Acid