Article (Scientific journals)
Valproic acid for the treatment of malignant gliomas: review of the preclinical rationale and published clinical results.
Berendsen, Sharon; Broekman, Marike; Seute, Tatjana et al.
2012In Expert Opinion on Investigational Drugs, 21 (9), p. 1391-415
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Keywords :
Animals; Antineoplastic Agents/adverse effects/pharmacology/therapeutic use; Brain Neoplasms/drug therapy/pathology; Clinical Trials as Topic; Combined Modality Therapy; DNA Repair/drug effects; Drug Evaluation, Preclinical; Glioblastoma/drug therapy/pathology; Glioma/drug therapy/pathology; Humans; Valproic Acid/adverse effects/pharmacology/therapeutic use
Abstract :
[en] INTRODUCTION: Glioblastoma multiforme is the most common and aggressive primary brain tumor. Valproate has been used as an anti-epileptic drug and mood stabilizer for decades. Recently, it was found to inhibit the proliferation of various cancers including glioblastoma multiforme. AREAS COVERED: We provide a comprehensive review of the mechanisms of action of valproate in gliomas, of its potential side effects and of the published clinical results obtained with this drug in glioblastomas. Valproate inhibits a subset of histone deacetylases and cellular kinases, and affects gene transcription through histone hyperacetylation, DNA hypomethylation and the modulation of several transcription factors. As a result, VPA induces differentiation of glioma cells, can prevent their invasion in surrounding tissues and may inhibit tumor angiogenesis. VPA can also inhibit DNA repair, thereby potentiating cytotoxic treatments such as chemotherapies or radiation therapy. Based on these mechanisms and case reports of glioblastoma remissions following VPA treatment, several clinical studies currently assess the therapeutic potential of VPA in glioma therapy. EXPERT OPINION: The combination of VPA treatment with chemotherapy and radiotherapy in glioblastoma appears a rational option that deserves well-designed prospective clinical trials that assess the efficacy and the molecular characteristics of the responding tumors in these patients.
Disciplines :
Genetics & genetic processes
Author, co-author :
Berendsen, Sharon
Broekman, Marike
Seute, Tatjana
Snijders, Tom
van Es, Corine
de Vos, Filip
Regli, Luca
Robe, Pierre ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Language :
English
Title :
Valproic acid for the treatment of malignant gliomas: review of the preclinical rationale and published clinical results.
Publication date :
2012
Journal title :
Expert Opinion on Investigational Drugs
ISSN :
1354-3784
eISSN :
1744-7658
Publisher :
Taylor & Francis, United Kingdom
Volume :
21
Issue :
9
Pages :
1391-415
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 15 January 2013

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