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Claudins:从上皮完整性的守门人到肝胰胆管癌的潜在靶点

英文原题:Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers.

查看英文原题

Claudins: from gatekeepers of epithelial integrity to potential targets in hepato-pancreato-biliary cancers.

PubMed 2024/09/26(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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中文摘要

Claudins 是一类四次跨膜蛋白家族,对上皮和内皮紧密连接的完整性至关重要,影响发育、分化和凋亡等细胞过程。Claudin 表达异常与多种恶性肿瘤相关,尤其影响组织结构,并可能促进肿瘤侵袭和转移。在这篇综合综述中,我们探讨 claudins 的多方面功能:其表达、在癌症中的特定作用(重点关注肝胰胆恶性肿瘤),并强调其作为治疗靶点的潜力。我们讨论当前的 claudin 靶向疗法,包括单克隆抗体、抗体-药物偶联物、双特异性 T 细胞衔接器和CAR-T 细胞疗法。这些方法在临床前和临床研究中显示出前景,尤其是在需求远未满足的肝胰胆癌症中。尽管有这些早期疗效迹象,但由于这些蛋白结构相似且功能重叠,有效靶向它们仍面临挑战。

展开英文摘要原文

Claudins, a family of tetraspan transmembrane proteins, are critical to the integrity of tight junctions in epithelia and endothelia, influencing cellular processes such as development, differentiation, and apoptosis. Abnormal claudin expression is associated with various malignancies, particularly affecting tissue architecture and potentially facilitating tumor invasion and metastasis.

In this comprehensive review, we explore the multifaceted functions of claudins: their expression, specific roles in cancer with a focus on hepato-pancreato-biliary malignancies and highlight their potential as therapeutic targets.

We discuss current claudin-targeted therapies, including monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engager and chimeric antigen receptor T-cell therapies. These approaches show promise in pre-clinical and clinical studies, particularly in hepato-pancreato-biliary cancers with large unmet needs. Despite these early signs of efficacy, challenges remain in effectively targeting these proteins due to their structural resemblance and overlapping functions.

论文信息

作者
Jeon H、Sterpi M、Mo C、Bteich F
单位
Department of Medical Oncology, Albert Einstein College of Medicine, Bronx, NY, United States.United States
文献类型
综述
期刊
Frontiers in oncology2024
原文标识
PubMed 39391254 · DOI 10.3389/fonc.2024.1454882