Cadherin-17 (CDH17) (CDH17)

Cadherin-17 (CDH17), also known as liver-intestine cadherin, is a non-classical member of the cadherin superfamily that functions as a calcium-dependent cell adhesion molecule and a proton-dependent peptide transporter. In healthy adults, its expression is highly restricted to the basolateral membranes of intestinal and pancreatic ductal epithelial cells, where it is often sequestered within tight junctions. However, CDH17 is frequently overexpressed and aberrantly localized on the surface of various gastrointestinal malignancies, including colorectal, gastric, and pancreatic cancers, as well as hepatocellular carcinoma. In the context of oncology, CDH17 acts as an oncogene by promoting tumor cell proliferation, migration, and metastasis through the activation of the Wnt/beta-catenin and integrin signaling pathways. Its high tumor specificity and cell-surface accessibility make it an attractive therapeutic target. Current drug development efforts focus on antibody-drug conjugates (ADCs), bispecific T-cell engagers, and CAR-T cell therapies designed to exploit the differential accessibility of CDH17 between malignant and healthy tissues to minimize off-target effects.

Other names

Liver-intestine cadherinLI-cadherinHPT-1Intestinal peptide-associated transporter HPT-17D-cadherinCadherin-17 (LI)

Drugs targeting CDH17 primarily utilize antibody-drug conjugates (ADCs) to deliver cytotoxic payloads directly to tumor cells, T-cell engagers (TCEs) or bispecific antibodies to redirect immune cells to the tumor, and chimeric antigen receptor (CAR) T-cell therapies to specifically eliminate CDH17-expressing malignant cells. Some agents also act as bispecific agonists (e.g., CDH17 x DR5) to induce apoptosis or as antagonists to disrupt oncogenic signaling pathways like Wnt/beta-catenin and integrin-mediated adhesion.