Translational research for hepatocellular carcinoma: What’s new?

Hepatocellular carcinoma (HCC) is a heterogeneous disease that usually develops within liver cirrhosis. Cancerogenesis in HCC is not a clear process and, at present, there is not a well-defined sequence of DNA mutations able to explain the entire process, from normal hepatocyte to HCC. Lately, the impact of some oncogenes on HCC development has been studied and some of these genes belong to the MAPKinases pathway, highlighting the importance of downstream effectors stimulated by the interaction between extracellular growth factors and tyrosine kinase receptors. Unfortunately, drugs able to interfere with the aforementioned pathway showed no positive results in clinical trials. A number of preclinical studies have focused the attention on epigenetic changes in HCC cells, focusing on the extensive DNA hypermetilation as a factor causing the knockout of several tumor suppressor genes. Cancerogenesis of HCC, at least at an early phase, could be sustained by epigenetic changes. Finally, some authors have tried to classify HCC on the basis of gene mutations found after performing an extensive genome sequencing, and interestingly, they have identified different classes of HCC on the basis of different clusters of mutated genes. HCC is not characterized by a unique driver mutation, as the case of EGFR mutations for lung cancer or K-Ras mutations for colorectal cancer, thus it is, at present, very difficult to identify a reliable target for antitumoral therapy. This review focuses on current translational research and molecular targets in the treatment of HCC.