title: New perspectives of valproic acid in clinical practice.
abstract: BACKGROUND
  Valproic acid (VPA) has been used in clinical practice as an anticonvulsant for more than four decades. Its pharmacokinetics and toxicity are thus well documented. VPA is also a potent class-selective histone deacetylase (HDAC) inhibitor at nontoxic therapeutic concentrations. New areas of application for VPA are currently opening up in clinical practice.
  
  
  METHODS
  The authors discuss VPA and how it may serve as an effective drug for cancer therapy. This is due to its ability to induce differentiation of a number of cancer cells in vitro and also to decrease tumor growth and metastases in animal models. The authors highlight how the utilization of VPA as an HDAC inhibitor is not limited to a single-agent therapy. Early clinical studies have also revealed promising potency of VPA in combination treatment with classic anticancer drugs. The authors do this by summarizing the published results and providing insight into the potential future developments for this field.
  
  
  CONCLUSIONS
  VPA was shown to restore or improve responsiveness of tumors to conventional therapeutic agents, to enhance the efficacy of adenoviral gene therapy, to sensitize TRAIL-resistant tumor cells to apoptosis, and to enhance radiosensitivity of tumor cells. Drawbacks in VPA medical applications include its teratogenicity and complexity of its effects.
authors.affiliation: Masaryk University, CEITEC - Central European Institute of Technology and Faculty of Science, Mendel Centre for Plant Genomics and Proteomics , Kamenice 753/5, CZ-62500 Brno , Czech Republic +420 549491466 ; +420 549492654 ; zdrahal@sci.muni.cz.
authors.forename: Lenka
authors.initials: L
authors.lastname: Činčárová
authors.forename: Zbyněk
authors.initials: Z
authors.lastname: Zdráhal
authors.forename: Jiří
authors.initials: J
authors.lastname: Fajkus
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid