CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cadherin 17 and digestive cancers: from diagnostic to therapeutic opportunities.
Cadherin 17 and digestive cancers: from diagnostic to therapeutic opportunities.
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Cadherin-17(CDH17,LI-cadherin)是一种非经典钙黏蛋白,在正常胃肠上皮中表达受限,正逐渐成为癌症中的多功能分子。CDH17 调控细胞间黏附,调节关键信号通路,并与肿瘤微环境相互作用,共同影响增殖、侵袭、转移、治疗耐药和免疫逃逸。其表达高度依赖背景并受到动态调控,上调和缺失均与肿瘤侵袭性和分化程度的不同特征相关。CDH17 还与调控干性和细胞可塑性的通路发生交互,提示其在调节治疗反应和耐药机制中发挥作用。除生物学功能外,CDH17 已被研究作为诊断标志物,基于组织的检测、循环生物标志物和放射性标记成像探针利用其肿瘤限制性表达和膜定位,为非侵入性肿瘤检测、分期和监测提供了机会。CDH17 还具有潜在的预后意义,尽管其临床相关性因分子背景和肿瘤分化状态而异,这强调需要进行整合性生物标志物评估。
最后,CDH17 的肿瘤特异性表达启发了多种治疗策略,包括细胞免疫疗法、抗体–药物偶联物、免疫毒素、放射性标记药物和工程化递送平台,所有这些策略均旨在选择性靶向表达 CDH17 的细胞,同时尽量减少脱靶毒性。这些策略凸显了 CDH17 作为治疗靶点和精准肿瘤学平台的转化潜力。在本综述中,我们总结了CDH17的分子机制、生物学功能、诊断和预后相关性以及治疗应用。通过整合当前研究成果并应对现有挑战,我们旨在全面概述其多方面作用,并强调利用该分子用于癌症临床应用的新兴策略。
Cadherin-17 (CDH17, LI-cadherin) is a non-classical cadherin with restricted expression in normal gastrointestinal epithelium, emerging as a multifunctional molecule in cancer. CDH17 regulates cell–cell adhesion, modulates key signaling pathways, and interacts with the tumor microenvironment, collectively influencing proliferation, invasion, metastasis, therapeutic resistance, and immune evasion. Its expression is highly context-dependent and dynamically regulated, with both upregulation and loss linked to distinct features of tumor aggressiveness and differentiation.
CDH17 also interfaces with pathways governing stemness and cellular plasticity, suggesting a role in modulating therapeutic response and resistance mechanisms. Beyond its biological functions, CDH17 has been investigated as a diagnostic marker, with tissue-based detection, circulating biomarkers, and radiolabeled imaging probes exploiting its tumor-restricted expression and membrane localization, offering opportunities for noninvasive tumor detection, staging, and monitoring.
CDH17 also holds potential prognostic significance, although its clinical relevance varies according to molecular context and tumor differentiation status, emphasizing the need for integrative biomarker assessment.
Finally, the tumor-specific expression of CDH17 has inspired multiple therapeutic strategies, including cellular immunotherapies, antibody–drug conjugates, immunotoxins, radiolabeled agents, and engineered delivery platforms, all designed to selectively target CDH17-expressing cells while minimizing off-target toxicity. Such strategies highlight the translational potential of CDH17 as both a therapeutic target and a platform for precision oncology.
In this review, we summarize the molecular mechanisms, biological functions, diagnostic and prognostic relevance, and therapeutic applications of CDH17. By integrating current findings and addressing existing challenges, we aim to provide a comprehensive overview of its multifaceted roles and to emphasize emerging strategies to harness this molecule for clinical applications in cancer.
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