CDH17: The Next Frontier in Gastrointestinal Cancer Therapy – HS-20110 ADC Inks $1.53B Roche Deal

CDH17: A Novel Tumor Target of Growing Interest in Recent YearsCDH17 (Cadherin 17), also known as Liver–intestine cadherin (LI-cadherin), or Human Peptide Transporter-1 (HPT-1), is an atypical member of the cadherin family, belonging to the 7-D subfamily. It features a long extracellular region containing seven Cadherin domains (EC1-EC7). Among these, EC1-EC2 are the distal membrane domains, or the N-terminal extracellular region, responsible for intercellular binding and most accessible for antibody recognition. The middle segment, EC3-EC5, may contribute to molecular flexibility and folding states, distinguishing between normal and tumor conformations. EC6 and EC7 are the proximal membrane domains, with EC6 containing the RGD motif, which exists in most mammals and mediates integrin recognition. CDH17 has a relatively short intracellular region and lacks the conserved cytoplasmic tail found in classical cadherins.

CDH17 Structure^[1]

CDH17 is primarily expressed in the gastrointestinal system, especially in colorectal enterocytes, Paneth cells, and goblet cells, functioning to mediate cell adhesion and maintain the integrity of epithelial cells. Additionally, as a proton-dependent peptide transporter, CDH17 promotes water absorption and regulates intestinal permeability. Meanwhile, CDH17 is a Ca²⁺Dependent cell adhesion molecules can initiate cell adhesion signals by binding to integrin molecules such as Integrin α2β1 and αIIbβ3, which is referred to as heterotypic interaction.

CDH17 Binds to Integrin α2β1^[2]

CDH17 can also mediate homotypic trans-interactions through different EC domains.^[3], participating in tight junctions and aggregation between cells. In tumor cells, these heterotypic and homotypic interaction capabilities may be simultaneously altered, leading to enhanced cell migration and adhesion abilities while weakening intercellular connections, causing cells to become detached and invasive.

Homotypic Trans Interaction of CDH17^[3]

CDH17 is highly expressed in a significant proportion of colorectal tumors and other gastrointestinal malignancies, including gastric cancer.^[4], Pancreatic Cancer^[5], Liver Cancer^[6], Neuroendocrine Tumors^[7]And carcinoid tumors. Compared with normal mucosa, the expression of CDH17 is usually relatively low in the early stages of cancer (such as colorectal cancer), but increases in the advanced stage, especially during liver metastasis. CDH17 has now become a star target for solid tumors, particularly gastrointestinal tumors, and due to its advantages such as high tumor specificity and membrane localization, it is very suitable as a target for targeted antibodies or ADCs.

Immobilized Human CDH17, His Tag at 1 μg/ml (100 μl/Well) on the plate. Dose response curve for Anti-CDH17 Antibody, hFc Tag with the EC₅₀ of 4.1 ng/ml determined by ELISA (QC Test).