Antineoplastic Effect of Valproic Acid: A Systematic Review of In Vivo Studies

Abstract

Background:: In recent years, cancer has become a noncommunicable disease with a high mortality in the world, constituting the second cause of death. Although it has a predominance of genetic abnormalities, molecular studies have shown that epigenetic alterations share a leading role in its development. Among the epigenetic drugs inhibiting deacetylases, we have valproic acid [VPA], a short-branched chain fatty acid with more than 50 years of clinical use. The potentialities of this drug that justify its use in antineoplastic therapy have been described recently. This drug offers the possibility of reversing some malignant characteristics of cancer cells, and it can be used in small, minimally toxic doses at low cost. Objective:: The aim of this study was to evaluate the use of valproic acid as an antineoplastic treatment in animal models. Methods:: A systematic review was conducted following the Prisma guidelines. Pubmed and Scopus were consulted for original articles that had evaluated the antineoplastic effect of VPA in vivo in the last 10 years. Results are presented in tables and graphs Results:: A total of 41 specific articles on the topic were selected. Few preclinical in vivo studies demonstrated the antineoplastic effects of VPA. Prostatic and hepatocellular carcinoma were the most common cancers in the consulted reports. Combination therapies using VPA with cytotoxic agents prevailed in this research, demonstrating a synergistic effect in reducing tumour volume. Conclusion:: VPA has an antineoplastic effect, and combination therapies show better results than monotherapies. However, more studies are required to confirm the usefulness of VPA as an adjuvant in the treatment of cancer.