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

IF 5.5 3区 材料科学 Q2 CHEMISTRY, PHYSICAL ACS Applied Energy Materials Pub Date : 2024-04-22 DOI:10.1055/s-0044-1785646
Antonio Saviano, Natascha Roehlen, Thomas F. Baumert
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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.
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作为治疗肝纤维化和肝细胞癌靶点的紧密连接蛋白
近十年来,暴露在肝细胞或癌细胞表面的紧密连接蛋白被发现是肝病生物学的介质:Claudin-1和Occludin是丙型肝炎病毒进入的宿主因子,Claudin-1已被确定为肝纤维化和肝细胞癌(HCC)的驱动因子。此外,Claudins 已成为肝病和 HCC 的治疗靶点。CLDN1 在肝纤维化和 HCC 中表达上调。针对 Claudin-1 的单克隆抗体(mAbs)已经完成了治疗肝纤维化和 HCC 的临床前概念验证研究,目前正在进行治疗晚期肝纤维化的临床开发。Claudin-6过表达与HCC侵袭性表型和耐药性有关。目前正在临床研究针对Claudin-6过表达肿瘤的Claudin-6 mAbs或嵌合抗原受体-T细胞疗法。总之,靶向 Claudin 蛋白为治疗晚期肝纤维化和 HCC 患者提供了一个新的临床机会。
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来源期刊
ACS Applied Energy Materials
ACS Applied Energy Materials Materials Science-Materials Chemistry
CiteScore
10.30
自引率
6.20%
发文量
1368
期刊介绍: ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.
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