From targets to targeted therapies in Hepatocellular carcinoma

Prognosis in advanced hepatocellular carcinoma (HCC) remains poor, despite the great improvement in the knowledge of the mechanisms behind hepatocarcinogenesis in recent years. Therapeutic options in the advanced stage of disease were quite limited until the introduction of sorafenib, a multi-kinase inhibitor. Sorafenib is considered the first systemic therapy and the only approved drug in advanced HCC. Unfortunately, sorafenib efficacy is rather limited in terms of overall survival, especially compared to results obtained with targeted therapies in other solid tumors; this limited efficacy is probably related to the heterogeneity of HCC. Consequently, a molecular characterization of HCC is urgently needed to improve treatments for and the clinical outcomes of HCC patients. This review offers a summary of the major studies regarding the signaling pathways involved in HCC pathogenesis, and an overview of the most promising drug treatments, apart from sorafenib, and the potential for their application in new therapeutic interventions in HCC.