Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities
Nikolaos Garmpis, Christos Damaskos, Anna Garmpi, Vasiliki Georgakopoulou, Panagiotis Sarantis, Efstathios Antoniou, Michalis V. Karamouzis, Afroditi Nonni, Dimitriοs Schizas, Evangelos Diamantis, Evangelos Koustas, Paraskevi Farmaki, Athanasios Syllaios, Alexandros Patsouras, Konstantinos Kontzoglou, Νικόλαος Τράκας, Dimitrios Dimitroulis
Abstract
Hepatocellular carcinoma (HCC) remains a major health problem worldwide with a continuous increasing prevalence. Despite the introduction of targeted therapies like the multi-kinase inhibitor sorafenib, treatment outcomes are not encouraging. The prognosis of advanced HCC is still dismal, underlying the need for novel effective treatments. Apart from the various risk factors that predispose to the development of HCC, epigenetic factors also play a functional role in tumor genesis. Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histone lysine residues of proteins, such as the core nucleosome histones, in this way not permitting DNA to loosen from the histone octamer and consequently preventing its transcription. Considering that HDAC activity is reported to be up-regulated in HCC, treatment strategies with HDAC inhibitors (HDACIs) showed some promising results. This review focuses on the use of HDACIs as novel anticancer agents and explains the mechanisms of their therapeutic effects in HCC.