Cadherin 17 and digestive cancers: from diagnostic to therapeutic opportunities

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.