Translational research for hepatocellular carcinoma: What’s new?

  • Salvatore Pisconti Medical Oncology Unit, POC SS Annunziata, Taranto, Italy.
  • Antonio Gnoni Medical Oncology Unit, Sacro Cuore Hospital, Gallipoli, Italy.
  • Giuseppina Della Vittoria Scarpati Medical Oncology Unit, POC SS Annunziata, Taranto, Italy.
  • Antonella Licchetta Medical Oncology Unit, Sacro Cuore Hospital, Gallipoli, Italy.
  • Nicola Silvestris Medical Oncology Unit, IRCCS Giovanni Paolo II, Bari, Italy.
  • Mario Giuliano Medical Oncology Unit, San Giovanni di Dio Hospital, ASL NA2 Nord, Naples, Italy.
  • Michele Montrone Medical Oncology Unit, POC SS Annunziata, Taranto, Italy.
  • Raffaele Addeo Lester and Sue Smith Breast Cancer Center, Houston, TX, United States.
  • Francesco Perri | francesco.perri80@alice.it Medical Oncology Unit, POC SS Annunziata, Taranto, Italy.
  • Antonio Giordano Department of Medicine, Division of Hematology & Oncology, Medical University of South Carolina, Charleston, SC, United States.

Abstract

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.

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Published
2017-10-30
Info
Issue
Section
Review Articles
Supporting Agencies
Holling Cancer Center's K12 Paul Calebresi Clinnical and Translational Oncology Training Program K12 CA157688
Keywords:
Hepatocellular carcinoma, Targeted therapy, Translational research, Epigenetics
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How to Cite
Pisconti, S., Gnoni, A., Della Vittoria Scarpati, G., Licchetta, A., Silvestris, N., Giuliano, M., Montrone, M., Addeo, R., Perri, F., & Giordano, A. (2017). Translational research for hepatocellular carcinoma: What’s new?. Translational Medicine Reports, 2(1). https://doi.org/10.4081/tmr.6902