Evolving anticancer drug valproic acid: insights into the mechanism and clinical studies.
The short chain fatty acid valproic acid (VPA) and VPA-analogs modulate the biology of diverse tumor cell entities by inducing differentiation, inhibiting proliferation, increasing apoptosis, and immunogenicity and by decreasing metastatic and angiogenetic potential. This review updates an earlier one in 2002, reflecting the interest in VPA as a potent anticancer drug. A number of in vitro studies show that the types of known tumor cells susceptible to VPA is steadily increasing. Of special note is the strong antineoplastic activity of VPA in chemoresistant cancer cells. A novel and promising approach is combining VPA with other drugs to achieve a broad therapeutic index. Clinical studies are underway and the preliminary results indicate that VPA alone or in combination offers a promising avenue of treatment, both in solid and hematopoetic malignancies.
Blaheta
Roman A
RA
Zentrum der Chirurgie, Klinik für Urologie und Kinderurologie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Michaelis
Martin
M
Driever
Pablo Hernáiz
PH
Cinatl
Jindrich
J
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy; D015534:Trans-Activators / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D051176:beta Catenin
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D015534:Trans-Activators; D051176:beta Catenin; D014635:Valproic Acid