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Hepatocellular carcinoma

Nature Reviews Disease Primers volume 2, Article number: 16018 (2016) | Download Citation

Abstract

Liver cancer is the second leading cause of cancer-related deaths globally and has an incidence of approximately 850,000 new cases per year. Hepatocellular carcinoma (HCC) represents approximately 90% of all cases of primary liver cancer. The main risk factors for developing HCC are well known and include hepatitis B and C virus infection, alcohol intake and ingestion of the fungal metabolite aflatoxin B1. Additional risk factors such as non-alcoholic steatohepatitis are also emerging. Advances in the understanding of the molecular pathogenesis of HCC have led to identification of critical driver mutations; however, the most prevalent of these are not yet druggable targets. The molecular classification of HCC is not established, and the Barcelona Clinic Liver Cancer staging classification is the main clinical algorithm for the stratification of patients according to prognosis and treatment allocation. Surveillance programmes enable the detection of early-stage tumours that are amenable to curative therapies — resection, liver transplantation or local ablation. At more developed stages, only chemoembolization (for intermediate HCC) and sorafenib (for advanced HCC) have shown survival benefits. There are major unmet needs in HCC management that might be addressed through the discovery of new therapies and their combinations for use in the adjuvant setting and for intermediate- and advanced-stage disease. Moreover, biomarkers for therapy stratification, patient-tailored strategies targeting driver mutations and/or activating signalling cascades, and validated measurements of quality of life are needed. Recent failures in the testing of systemic drugs for intermediate and advanced stages have indicated a need to refine trial designs and to define novel approaches.

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Acknowledgements

J.M.L. has grants from the US National Cancer Institute (NCI) (P30CA165979), the European Commission Horizon 2020 (HEP-CAR, proposal number 667273–2), the Samuel Waxman Cancer Research Foundation, the Grant I+D Program (SAF2013-41027) and the Asociación Española Contra el Cáncer (AECC). J.Z.-R. has received funding from INSERM, the French National Cancer Institute (INCa) and The Ligue Contre le Cancer (équipe Labellisée). E.P. receives funding from the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the European Research Council and the Israel Science Foundation. The authors thank R. Montal, S. Torrecilla, A. Farré and M. Boteller (Liver Cancer Translational Research Laboratory, BCLC Group, IDIBAPS — Hospital Clinic, Barcelona, Spain) for their support in editing references, figures and tables for this manuscript.

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Affiliations

  1. Liver Cancer Program, Division of Liver Diseases and RM Transplant Institute, Tisch Cancer Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, Madison Avenue 1425, 11F-70, Box 1123, New York, New York 10029, USA.

    • Josep M. Llovet
    •  & Myron Schwartz
  2. Liver Cancer Translational Research Laboratory, Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, IDIBAPS - Hospital Clinic, CIBERehd, University of Barcelona, Catalonia, Spain.

    • Josep M. Llovet
  3. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Catalonia, Spain.

    • Josep M. Llovet
  4. INSERM, UMR-1162, Génomique Fonctionnelle des Tumeurs Solides, Equipe Labellisée Ligue Contre le Cancer, Institut Universitaire d'Haematologie, Paris, France.

    • Jessica Zucman-Rossi
  5. Université Paris Descartes, Labex Immuno-Oncology, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.

    • Jessica Zucman-Rossi
  6. Université Paris 13, Sorbonne Paris Cité, Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine, Bobigny, France.

    • Jessica Zucman-Rossi
  7. Université Paris Diderot, Paris, France.

    • Jessica Zucman-Rossi
  8. Lautenberg Center for Immunology and Cancer Research and Department of Pathology, Hebrew University Hadassah-Medical School, Jerusalem, Israel.

    • Eli Pikarsky
  9. Liver Unit, Clínica Universidad de Navarra, Pamplona, Spain.

    • Bruno Sangro
  10. Instituto de Investigación Sanitaria de Navarra (IDISNA) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Pamplona, Spain.

    • Bruno Sangro
  11. Department of Gastroenterology, University Health Network, University of Toronto, Toronto, Ontario, Canada.

    • Morris Sherman
  12. Mayo Clinic, Mayo College of Medicine, Rochester, Minnesota, USA.

    • Gregory Gores

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Contributions

Introduction (J.M.L.); Epidemiology (G.G.); Mechanisms/pathophysiology (J.Z.-R. and E.P.); Diagnosis, screening and prevention (M.Sh. and G.G.); Management (M.Sc., B.S. and J.M.L.); Quality of life (M.Sh.); Outlook (J.M.L., G.G. and E.P.); overview of Primer (J.M.L.).

Competing interests

J.M.L. receives research support and grants from Bayer Pharmaceuticals, Blueprint Medicines, Bristol-Myers Squibb and Boehringer Ingelheim, and is a consultant for Bayer Pharmaceuticals, Bristol-Myers Squibb, Blueprint Medicines, Eli Lilly and Company, Celsion, Biocompatibles, Boehringer Ingelheim, Novartis and GlaxoSmithKline. M.Sh. is a consultant for Bayer Pharmaceuticals, Celsion, ArQule, H3 Biomedicine and Merck. J.Z.-R. is a consultant for IntegraGen. B.S. has received lecturing and consulting fees from Bayer Healthcare and Sirtex Medical. G.G. is in the Data Safety and Monitoring committee for a Bayer Pharmaceuticals trial in hepatocellular carcinoma. M.Sc. and E.P. have nothing to disclose.

Corresponding author

Correspondence to Josep M. Llovet.

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https://doi.org/10.1038/nrdp.2016.18