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Semin Liver Dis
DOI: 10.1055/s-0044-1785646
Review Article

Tight Junction Proteins as Therapeutic Targets to Treat Liver Fibrosis and Hepatocellular Carcinoma

Antonio Saviano
1   Inserm, U1110, Institute of Translational Medicine and Liver Disease, Strasbourg, France
2   University of Strasbourg, Strasbourg, France
3   Service d'hépato-gastroentérologie, Pôle Hépato-digestif, Institut-Hospitalo-Universitaire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
,
Natascha Roehlen
4   Department of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
5   Berta-Ottenstein-Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany
,
Thomas F. Baumert
1   Inserm, U1110, Institute of Translational Medicine and Liver Disease, Strasbourg, France
2   University of Strasbourg, Strasbourg, France
3   Service d'hépato-gastroentérologie, Pôle Hépato-digestif, Institut-Hospitalo-Universitaire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
6   Institut Universitaire de France, Paris, France
› Institutsangaben Funding The authors acknowledge the following financial support: European Research Council Grant ERC-AdG-2014 HEPCIR (T.F.B.); European Research Council Grant ERC-AdG-2020 FIBCAN (T.F.B.); European Research Council Grant ERC-PoC-2016 PRELICAN (T.F.B.); European Research Council Grant ERC-PoC-2018 HEPCAN (T.F.B.); ARC Grant TheraHCC2.0 IHUARC IHU201301187 (T.F.B.); ANRS Grant ECTZ103701 (T.F.B.); SATT Conectus, University of Strasbourg (CANCLAU) (T.F.B.); French National Research Agency DELIVER (ANR-21-RHUS-0001) within the France 2030 program and LABEX ANR-10-LABX-0028_HEPSYS (T.F.B.); Berta Ottenstein Program of the University Freiburg (N.R.). This work of the Interdisciplinary Thematic Institute IMCBio, as part of the ITI 2021–2028 program of the University of Strasbourg, CNRS, and Inserm, was further supported by IdEx Unistra (ANR-10-IDEX-0002), and by SFRI-STRAT'US project (ANR 20-SFRI-0012) and EUR IMCBio (ANR-17-EURE-0023) under the framework of the French Investments for the Future Program and the France 2030 program.
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Abstract

In the last decade tight junction proteins exposed at the surface of liver or cancer cells have been uncovered as mediators of liver disease biology: Claudin-1 and Occludin are host factors for hepatitis C virus entry and Claudin-1 has been identified as a driver for liver fibrosis and hepatocellular carcinoma (HCC). Moreover, Claudins have emerged as therapeutic targets for liver disease and HCC. CLDN1 expression is upregulated in liver fibrosis and HCC. Monoclonal antibodies (mAbs) targeting Claudin-1 have completed preclinical proof-of-concept studies for treatment of liver fibrosis and HCC and are currently in clinical development for advanced liver fibrosis. Claudin-6 overexpression is associated with an HCC aggressive phenotype and treatment resistance. Claudin-6 mAbs or chimeric antigen receptor-T cells therapies are currently being clinically investigated for Claudin-6 overexpressing tumors. In conclusion, targeting Claudin proteins offers a novel clinical opportunity for the treatment of patients with advanced liver fibrosis and HCC.

Keywords

Claudins - monoclonal antibodies - therapeutic target - signaling - cell plasticity

Authors' Contribution

A.S. conceptualized, wrote the manuscript, and prepared the figures. N.R. wrote the manuscript. T.F.B. conceptualized, wrote, and edited the manuscript.




Publikationsverlauf

Artikel online veröffentlicht:
22. April 2024

© 2024. Thieme. All rights reserved.

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