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Carcinome hépatocellulaire : nouveaux concepts, nouvelles molécules et nouvelles approches

Hepatocellular carcinoma: New concepts, new drugs and new approaches

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Oncologie

Résumé

Les connaissances biologiques récentes sur le carcinome hépatocellulaire (CHC) ont permis de souligner sa complexité. Le rôle important de la vascularisation tumorale a conduit à mettre en évidence l’activité du sorafénib, et plus récemment du régorafénib pour les formes avancées de CHC. Le microenvironnement a gagné en importance ces dernières années dans le développement d’autres cibles thérapeutiques, notamment pour les approches d’immunothérapie qui sont en cours d’exploration dans cette pathologie. Nous sommes certainement à l’aube du développement d’autres concepts innovants qui seront discutés dans cette revue.

Abstract

Recent biological knowledge on hepatocellular carcinoma (HCC) has underlined the complexity of this malignant disease. The crucial role of tumor angiogenesis gave way to the use of sorafenib, and more recently, regorafenib showed activity for advanced stages of HCC. The microenvironment gained interest in recent years for the development of targeted therapies in HCC, particularly for immunotherapy approaches that are currently being investigated as therapies for this malignant disease. Hopefully, this is only the beginning of a new era exploring other innovative concepts, which will be discussed in this review.

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Références

  1. Llovet JM, Zucman-Rossi J, Pikarsky E, et al (2016) Hepatocellular carcinoma. Nat Rev Dis Primers 2:16018

    Article  PubMed  Google Scholar 

  2. Hernandez-Gea V, Toffanin S, Friedman SL, et al (2013) Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology 144:512–27

    Article  PubMed  PubMed Central  Google Scholar 

  3. Rani B, Cao Y, Malfettone A, et al (2014) Role of the tissue microenvironment as a therapeutic target in hepatocellular carcinoma. World J Gastroenterol 20:4128–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wu SD, Ma YS, Fang Y, et al (2012) Role of the microenvironment in hepatocellular carcinoma development and progression. Cancer Treat Rev 38:218–25

    Article  CAS  PubMed  Google Scholar 

  5. Nishida N, Kudo M (2017) Immunological microenvironment of hepatocellular carcinoma and its clinical implication. Oncology 92:40–9

    Article  PubMed  Google Scholar 

  6. Coulouarn C, Corlu A, Glaise D, et al (2012) Hepatocyte-stellate cell cross-talk in the liver engenders a permissive inflammatory microenvironment that drives progression in hepatocellular carcinoma. Cancer Res 72:2533–42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Giannelli G, Rani B, Dituri F, et al (2014) Moving towards personalised therapy in patients with hepatocellular carcinoma: the role of the microenvironment. Gut 63:1668–76

    Article  CAS  PubMed  Google Scholar 

  8. Semela D, Dufour JF (2004) Angiogenesis and hepatocellular carcinoma. J Hepatol 41:864–80

    Article  PubMed  Google Scholar 

  9. Ye LY, Chen W, Bai XL, et al (2016) Hypoxia-induced epithelialto-mesenchymal transition in hepatocellular carcinoma induces an immunosuppressive tumor microenvironment to promote metastasis. Cancer Res 76:818–30

    Article  CAS  PubMed  Google Scholar 

  10. Sia D, Villanueva A, Friedman SL, et al (2017) Liver cancer cell of origin, molecular class, and effects on patient prognosis. Gastroenterology 152:745–61

    Article  CAS  PubMed  Google Scholar 

  11. Llovet JM, Ricci S, Mazzaferro V, et al (2008) Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359:378–90

    Article  CAS  PubMed  Google Scholar 

  12. Cheng AL, Kang YK, Chen Z, et al (2009) Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:25–34

    Article  CAS  PubMed  Google Scholar 

  13. Bruix J, Qin S, Merle P, et al (2017) Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebocontrolled, phase III trial. Lancet 389:56–66

    Article  CAS  PubMed  Google Scholar 

  14. El-Khoueiry AB, Sangro B, Yau T, et al (2017) Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase I/II dose escalation and expansion trial. Lancet (published online Apr 20)

    Google Scholar 

  15. Santoro A, Rimassa L, Borbath I, et al (2013) Tivantinib for second-line treatment of advanced hepatocellular carcinoma: a randomised, placebo-controlled phase II study. Lancet Oncol 14:55–63

    Article  CAS  PubMed  Google Scholar 

  16. Faivre S, Blanc JF, Merle P, et al (2016) Tolerability and activity of second-line tepotinib, a potent and highly selective c-MET inhibitor, in patients with advanced hepatocellular carcinoma previously treated with sorafenib. Ann Oncol 27:ii109

    Article  PubMed Central  Google Scholar 

  17. Faivre SJ, Santoro A, Kelley RK, et al (2014) A phase II study of a novel transforming growth factor-beta (TGF-ß1) receptor I kinase inhibitor, LY2157299 monohydrate (LY), in patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 32 (abstract LBA173)

    Google Scholar 

  18. Faivre S, Bouattour M, Dreyer C, et al (2009) Sunitinib in hepatocellular carcinoma: redefining appropriate dosing, schedule, and activity end points. J Clin Oncol 27:e248–e50

    Article  CAS  PubMed  Google Scholar 

  19. Bouattour M, Rousseau B, Wassermann J, et al (2015) Negative trials for foreseeable safety reasons in advanced hepatocellular carcinoma: how long are we going to take lightly pharmacokinetics of tyrosine kinase inhibitors? J Clin Oncol 33:2484–5

    Article  PubMed  Google Scholar 

  20. Llovet JM, Hernandez-Gea V (2014) Hepatocellular carcinoma: reasons for phase III failure and novel perspectives on trial design. Clin Cancer Res 20:2072–9

    Article  CAS  PubMed  Google Scholar 

  21. Faivre S, de Gramont A, Raymond E (2016) Learning from 7 years of experience with sorafenib in advanced HCC: sorafenib better than sorafenib? Targeted Oncol 11:565–67

    Article  Google Scholar 

  22. Wilhelm SM, Dumas J, Adnane L, et al (2011) Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 129:245–55

    Article  CAS  PubMed  Google Scholar 

  23. Bruix J, Tak WY, Gasbarrini A, et al (2013) Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. Eur J Cancer 49:3412–19

    Article  CAS  PubMed  Google Scholar 

  24. Kudo M (2016) Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 5:235–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ishida Y, Agata Y, Shibahara K, et al (1992) Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO 11:3887–95

    CAS  Google Scholar 

  26. Kelley RK, Verslype C, Cohn AL et al (2017) Cabozantinib in hepatocellular carcinoma: results of a phase II placebo-controlled randomized discontinuation study. Ann Oncol 28:528–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Qin S, Lim HY, Ryoo BY, et al (2016) Tolerability and activity of tepotinib in Asian patients with advanced hepatocellular carcinoma (HCC). J Clin Oncol 34 (abstract 4072)

    Google Scholar 

  28. Mellor HR (2014) Targeted inhibition of the FGF19-FGFR4 pathway in hepatocellular carcinoma; translational safety considerations. Liver Int 34:e1–e9

    Article  CAS  PubMed  Google Scholar 

  29. Hagel M, Miduturu C, Sheets M, et al (2015) First selective small molecule inhibitor of FGFR4 for the treatment of hepatocellular. Cancer Discov 5:424–37

    Article  CAS  PubMed  Google Scholar 

  30. Achyut BR, Yang L (2011). Transforming growth factor-ß in the gastrointestinal and hepatic tumor microenvironment. Gastroenterology 141:1167–78

    Article  CAS  PubMed  Google Scholar 

  31. Serova M, Tijeras-Raballand A, Dos Santos C, et al (2015) Effects of TGF-beta signalling inhibition with galunisertib (LY2157299) in hepatocellular carcinoma models and in ex vivo whole tumor tissue samples from patients. Oncotarget 6:21614–27

    Article  PubMed  PubMed Central  Google Scholar 

  32. Wassermann J, Bouattour M, Dreyer C, et al (2012) Thérapies ciblées dans le carcinome hépatocellulaire: indications et perspectives. Oncologie 14:179–85

    Article  CAS  Google Scholar 

  33. (2013) Breakthrough of the year 2013. How we did in 2013 and… Science 342:1442

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Authors and Affiliations

  1. Oncologie médicale et digestive, hôpital Beaujon, HUPVNS et université Paris-VII, 100, boulevard du Général Leclerc, F-92110, Clichy, France

    M. Bouattour & S. Faivre

  2. Oncologie médicale, groupe hospitalier Saint-Joseph, 185, rue Raymond Losserand, F-75014, Paris, France

    E. Raymond

Authors
  1. M. Bouattour
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  2. E. Raymond
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  3. S. Faivre
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Corresponding author

Correspondence to S. Faivre.

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Bouattour, M., Raymond, E. & Faivre, S. Carcinome hépatocellulaire : nouveaux concepts, nouvelles molécules et nouvelles approches. Oncologie 19, 168–176 (2017). https://doi.org/10.1007/s10269-017-2712-2

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  • DOI: https://doi.org/10.1007/s10269-017-2712-2

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