CDH17: The Next Breakthrough in Gastrointestinal Cancer Therapy

On October 17, 2025, Hansoh Pharmaceutical granted Roche the global rights (excluding Greater China) to its investigational CDH17-targeting ADC drug, HS-20110. Under the agreement, Roche will pay an upfront payment of USD 80 million and milestone payments of up to $1.45 billion bringing the total deal up to $1.53 billion in upfront and milestone payments, plus royalties.  This transaction highlights the strong druggability, differentiated competitiveness, and significant commercial potential of CDH17 as a target.  Currently, HS-20110 is in a Phase I clinical trial.

CDH17: A next-generation major target for solid tumors with both structural and functional advantages.

In recent years, CDH17 has emerged as a new and highly promising tumor target. Its unique structural features and abnormally high expression in gastrointestinal tumors distinguish it among other adhesion molecules, making it a critical bridge between structural biology and precision medicine.  CDH17 (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 7D subfamily. It possesses a relatively long extracellular region composed of seven cadherin domains (EC1–EC7):

• EC1–EC2: These distal, N-terminal extracellular domains are the most exposed regions, making them prime targets for antibody recognition. These regions do not mediate cell-cell adhesion using the same mechanism traditional cadherin family proteins do. Rather, EC2 and EC4 interact with each other in complex between monomers to mediate cell adhesion [3]. 

• EC3–EC5: These mid-region domains do not seem to participate directly in adhesion/integrin binding but rather may contribute to structural flexibility and folding, potentially differentiating normal conformation versus tumor-specific conformations.

• EC6–EC7: These membrane-proximal domains include EC6, which contains an RGD motif conserved across many mammals and mediates integrin recognition.

The intracellular region of CDH17 is short and lacks the conserved cytoplasmic tail typical of classical cadherins. This structure informs both its therapeutic accessibility and its role in tumor-specific biology.

The Structure of CDH17 [1]

CDH17 is primarily expressed in the gastrointestinal system, especially in colorectal epithelial cells, Paneth cells, and goblet cells, where it functions to mediate cell–cell adhesion and maintain epithelial integrity. CDH17 has also been reported to act as a proton-dependent peptide transporter in intestinal epithelia and to be associated with water absorption and regulation of intestinal permeability, although its transporter activity remains incompletely characterized. Furthermore, it is a Ca²⁺-dependent cell adhesion molecule, capable of interacting with integrins such as Integrin α2β1, thereby initiating cell adhesion signaling, a phenomenon referred to as heterotypic interaction.

CDH17 binding to Integrin α2β1[2]

CDH17 can also mediate homophilic trans interactions through its different EC domains, contributing to cellular aggregation [3]. In tumor cells, both heterotypic and homophilic interactions are compromised, leading to enhanced cell migration and adhesion changes, weakened intercellular connections, cell detachment and invasion.

The homophilic trans-interaction of CDH17 [3]

CDH17 is highly expressed in a significant portion of colorectal cancers and other gastrointestinal malignancies, including gastric cancer, pancreatic cancer, liver cancer, neuroendocrine tumors, and carcinoid tumors [4,5,6,7]. Generally, compared with normal mucosa, CDH17 expression is relatively low in early-stage cancers (e.g., colorectal cancer) but increases in later stages, particularly during liver metastasis. Nowadays, CDH17 has emerged as a new prominent target in solid tumors, especially gastrointestinal cancers. Its high tumor specificity and membrane localization make it an ideal target for antibody-based therapies or ADCs.

Design and strategic deployment of CDH17-targeted therapies

Targeted drug development against CDH17 is advancing rapidly, with ADCs currently representing the most actively pursued modality. Besides Hansoh’s HS-20110, other notable ADC candidates include 7MW4911 (Mabwell), SIM0609 (Simcere), and MRG007 (Lepu Biopharma). Additional strategies, such as bispecific antibodies and bispecific ADCs (e.g., Novartis [8]), trispecific antibodies, and cell therapies, are also being explored, highlighting the definitive therapeutic potential and broad translational prospects of CDH17 in gastrointestinal cancers.

Many of these drugs mentioned above are thought to target the EC1–EC2 domains of CDH17, such as 7MW4911 [9]. These distal, membrane-exposed epitopes may enhance ADC internalization and improve drug accessibility and binding efficiency. Some candidates, however, may target other EC regions; for example, Arbele’s TCE ARB202 may be designed against EC5–EC7 to block CDH17–integrin interactions and prevent shedding of the extracellular domain as one patent suggests. Thus, the extracellular domains (EC1–EC7) of CDH17 determine the mechanism of action and selectivity of therapeutic drugs. 

Clinical progression of CDH17-targeted drugs.

In summary, the domain-specific development strategy is now becoming a critical basis for the precise design of CDH17-targeted drugs, paving the way for multi-mechanistic and diversified combination therapies, enhancing the durability of CDH17-targeted therapy.

High-quality tool proteins are the foundation of targeted drug development. KACTUS has independently designed and developed highly active recombinant CDH17 proteins, exclusively offering products that cover all extracellular domains (EC1–EC7) of CDH17. All products have undergone rigorous quality testing and are suitable for a variety of applications, including animal immunization, antibody screening, and epitope mapping.

Product Validation Data:

Immobilized Human CDH17 Domain 1&2, His Tag at 1μg/ml (100μl/well) on the plate. Dose response curve for Anti-CDH17 Antibody, hFc Tag with the EC50 of 4.7ng/ml determined by ELISA (QC Test).

Immobilized Human CDH17 Domain 5-7, His Tag at 0.5μg/ml (100μl/well) on the plate. Dose response curve for Anti-CDH17 Domain 5-7 Antibody, hFc Tag with the EC50 of 7.1ng/ml determined by ELISA. (QC Test)

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)

Product List

References:

[1] Immunoaffinity enrichment LC-MS/MS quantitation of CDH17 in tissues. Bioanalysis. 2020 Oct;12(20):1439-1447. doi: 10.4155/bio-2020-0162.

[2] An RGD motif present in cadherin 17 induces integrin activation and tumor growth. J Biol Chem. 2014 Dec 12;289(50):34801-14. doi: 10.1074/jbc.M114.600502.

[3] Mechanism of dimerization and structural features of human LI-cadherin. J Biol Chem. 2021 Aug 6;297(3):101054. doi: 10.1016/j.jbc.2021.101054

[4] CDH17 Is a More Sensitive Marker for Gastric Adenocarcinoma Than CK20 and CDX2. Arch Pathol Lab Med. 2017 Jan;141(1):144-150. doi: 10.5858/arpa.2015-0404-OA.

[5] Identification and Validation of Novel Subtype-Specific Protein Biomarkers in Pancreatic Ductal Adenocarcinoma. Pancreas. 2017 Mar;46(3):311-322. doi: 10.1097/MPA.0000000000000743.

[6] Targeting cadherin-17 inactivates Wnt signaling and inhibits tumor growth in liver carcinoma. Hepatology. 2009 Nov;50(5):1453-63. doi: 10.1002/hep.23143.

[7] Expression of cadherin 17 in well-differentiated neuroendocrine tumours. Histopathology. 2015 Jun;66(7):1010-21. doi: 10.1111/his.12610. Epub 2015 Jan 13.

[8] A bispecific antibody-drug conjugate targeting pCAD and CDH17 has antitumor activity and improved tumor-specificity. MAbs. 2025 Dec;17(1):2441411. doi: 10.1080/19420862.2024.2441411.

[9] Overcoming multidrug resistance in gastrointestinal cancers with a CDH17-targeted ADC conjugated to a DNA topoisomerase inhibitor. Cell Rep Med. 2025 Jul 1;6(7):102213. doi: 10.1016/j.xcrm.2025.102213

[10] Global Disparities in Colorectal Cancer: Unveiling the Present Landscape of Incidence and Mortality Rates, Analyzing Geographical Variances, and Assessing the Human Development Index. J Prev Med Hyg. 2025 Jan 31;65(4):E499–E514. doi: 10.15167/2421-4248/jpmh2024.65.4.3071

[11] Analysis of trends in the burden of colorectal cancer in China and globally from 1990 to 2021 with projections for the next 15 years: a cross-sectional study based on the GBD database. Front Public Health. 2025 Jun 27:13:1635228. doi: 10.3389/fpubh.2025.1635228.

[12] CDX2 regulates liver intestine-cadherin expression in normal and malignant colon epithelium and intestinal metaplasia. Gastroenterology. 2002 Nov;123(5):1565-77. doi: 10.1053/gast.2002.36598.

[13] Beyond N-Cadherin, Relevance of Cadherins 5, 6 and 17 in Cancer Progression and MetastasisInt J Mol Sci. 2019 Jul 9;20(13):3373. doi: 10.3390/ijms20133373.

[14] Crystal structure of the nonclassical cadherin-17 N-terminus and implications for its adhesive binding mechanism. Acta Cryst F. 2021 Mar;77(Pt 3):85–94. doi:10.1107/S2053230X21002247