浅述Nectin4作为肿瘤靶点在诊断与治疗中的 应用与挑战

Applications and Challenges of Nectin4 as a Tumor Target in Cancer Diagnosis and Therapy

摘要: Nectin4是一种在多种实体瘤中异常上调的免疫球蛋白样黏附分子，在肿瘤细胞黏附、迁移、侵袭及免疫调节中发挥重要作用，已成为肿瘤精准诊疗的重要潜在靶点。随着分子影像学和靶向治疗技术的快速发展，新型小分子配体与核酸适体因其分子量小、特异性高、结构易修饰、免疫原性低等优势，在肿瘤靶向诊断与药物递送领域呈现出显著潜力。本文系统梳理了Nectin4的结构特点、信号通路及其在肿瘤中的表达与预后关联，综述目前围绕Nectin4的诊断研究，包括抗体及抗体偶联物、核酸适体成像探针以及小分子靶向探针的发展现状。在治疗方向上，总结了基于Nectin4的抗体药物、适体递药系统、小分子靶向策略的应用进展，并分析核酸适体与小分子在多维度互补下构建新型精准诊疗体系的可行性。整体来看，核酸适体与小分子为Nectin4靶向诊疗提供了更灵活、安全且具有成像与治疗双重潜力的分子工具，为未来实现肿瘤的早期识别、精准治疗和诊疗一体化奠定了重要基础。

Abstract: Nectin4 is an immunoglobulin-like cell adhesion molecule that is aberrantly upregulated in various solid tumors and plays important roles in tumor cell adhesion, migration, invasion, and immune regulation, making it a potential target for precision cancer diagnosis and therapy. With the rapid development of molecular imaging and targeted therapeutic strategies, small-molecule ligands and nucleic acid aptamers have attracted increasing attention due to their small molecular size, high specificity, structural flexibility, and low immunogenicity. This review summarizes the structural characteristics and signaling functions of Nectin4, as well as its expression patterns and prognostic relevance in different malignancies. Current diagnostic approaches targeting Nectin4 are discussed, including antibody-based probes and antibody-drug conjugates, while emerging strategies involving aptamer-based imaging agents and small-molecule targeting probes are critically evaluated. In the therapeutic context, recent advances in Nectin4-directed antibody therapies are reviewed, and the potential of aptamer-mediated drug delivery and small-molecule targeting strategies is discussed. Importantly, this article emphasizes that, despite their theoretical advantages, both nucleic acid aptamers and small-molecule ligands targeting Nectin4 remain at an early stage of development, with a lack of well-characterized lead compounds representing a major bottleneck in the field. In the therapeutic context, this work summarizes the application progress of Nectin4-based antibody drugs, aptamer-mediated drug delivery systems, and small-molecule targeting strategies, and analyzes the feasibility of constructing a novel precision diagnostic and therapeutic framework through the multidimensional complementarity of nucleic acid aptamers and small molecules. Overall, nucleic acid aptamers and small molecules provide more flexible and safer molecular tools with dual imaging and therapeutic potential for Nectin4-targeted diagnosis and therapy, laying an important foundation for the future realization of early tumor detection, precision treatment, and integrated theranostics.