New perspectives of valproic acid in clinical practice

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Authors

ČINČÁROVÁ Lenka ZDRÁHAL Zbyněk FAJKUS Jiří

Year of publication 2013
Type Article in Periodical
Magazine / Source Expert Opinion on Investigational Drugs
MU Faculty or unit

Central European Institute of Technology

Citation
Web Full Text
Doi http://dx.doi.org/10.1517/13543784.2013.853037
Field Oncology and hematology
Keywords CAR; combination therapy; HDAC inhibition; radiosensitization; TRAIL/Apo2L; valproic acid
Attached files
Description Introduction: 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. Areas covered: 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. Expert opinion: 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.
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