The Rise of the CDH6 Target: Next-Generation ADC Drugs Lead New Breakthroughs in Ovarian Cancer Treatment
By Lauren He
July 1, 2026
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Human Cadherin-6 (CDH6), as a member of the type II classical cadherin family, exhibits specific high expression in various malignant tumors, demonstrating immense therapeutic potential, especially in refractory tumors such as ovarian cancer and renal cell carcinoma. Currently, there are no approved targeted therapies for CDH6 globally, but several antibody-drug conjugates (ADCs) have entered clinical research stages, bringing new hope to patients with these refractory tumors.
CDH6 Target Characteristics: Biological Features and Therapeutic Value
CDH6 is a single-pass transmembrane protein composed of 790 amino acids, and its encoding gene is located on chromosome 5. Unlike other type II classical cadherins, CDH6 contains a unique RGD motif in the EC1 domain and a HAV motif in the EC5 domain; these characteristic domains play key roles in stabilizing protein structure and mediating cell-cell adhesion. Like other classical cadherins, the cytoplasmic tail of CDH6 can bind to p120-catenin and β-catenin to regulate the actin cytoskeleton. Due to the core role of β-catenin in the Wnt signaling pathway, there is a link between β-catenin signaling and CDH6-mediated intercellular adhesion[1], which provides important clues for understanding its role in tumor development and progression.
Figure 1. Structural diagram of human cadherin family members[2]
During development, CDH6 is specifically expressed in the brain and kidneys, playing a crucial role in the formation of central nervous system circuits. Its expression profile is particularly distinct: it has limited expression in normal adult tissues, mainly confined to proximal renal tubules and bile duct epithelial cells. In addition, CDH6 is also expressed in platelets, playing a functional role in platelet aggregation and thrombosis. Notably, CDH6 is overexpressed in various malignant tumors, especially in refractory tumors like ovarian cancer and renal cell carcinoma. This expression characteristic provides an ideal therapeutic window for CDH6-targeted therapy.
Figure 2. A. Differences in CDH6 expression between normal tissue and cancer tissue samples (red boxes indicate renal cancer and ovarian cancer). B. CDH6 protein expression in clinical primary renal cancer and ovarian cancer samples assessed by IHC[3]
Currently, the mechanism of action of CDH6 in cancer is not yet fully understood. Studies have shown that CDH6 binds to the αIIbβ3 integrin through the RGD motif, activates the α2β1 integrin, and promotes the adhesion, invasion, and lung metastasis of ovarian cancer and renal cancer via signaling pathways such as SRC and FAK[4].
Figure 3. Signaling pathways by which CDH6 induces cancer cell invasion and metastasis[4]
CDH6 Drug Development Progress: Multiple ADC Drugs in Fierce Competition
There are currently 14 therapies targeting CDH6 under development globally, of which 5 have entered clinical research stages, all being ADC drugs. The fastest-progressing among them is Daiichi Sankyo's Raludotatug deruxtecan, which has advanced to Phase 2/3 clinical studies.
Examples of CDH6 ADC in development
Daiichi Sankyo/Merck (DS-6000)
Raludotatug deruxtecan (DS-6000 or R-DXd) is a CDH6-targeted ADC drug developed by Daiichi Sankyo. Its conjugation still utilizes the "MC + GGFG tetrapeptide + self-immolative spacer + DXd structure," with a DAR value of approximately 8. Notably, compared to Novartis's discontinued HKT288, the unique aspect of DS-6000 lies in its precise targeting of the EC3 domain of the CDH6 protein, which constitutes a fundamental difference in their mechanisms of action[5].
Figure 4. Structural diagram of DS-6000[5]
As the frontrunner, Daiichi Sankyo's DS-6000 has advanced to Phase 2/3 clinical trials. Its Phase 1 study results showed an ORR of 38% and a disease control rate of 98% in patients with platinum-resistant ovarian cancer, demonstrating significant clinical potential. The $22 billion collaboration agreement between Merck and Daiichi Sankyo is a strong endorsement of the commercial value of the CDH6 target. Domestic enterprises are also actively laying out their plans; Qilu Pharmaceutical's QLS5133, Puzhong Discovery's CUSP06, Simcere Zaiming's SIM0505, and Hansoh Pharma's HS-20124 have all entered the clinical research stage, forming a healthy competitive landscape. In particular, the strong "bystander effect" demonstrated by CUSP06 provides a new solution for overcoming tumor heterogeneity. With the accumulation of more clinical data and the expansion of indications, CDH6-targeted drugs are expected to become an important supplement in the field of oncology, especially with significant advantages in precision medicine and personalized treatment.
KACTUS CDH6 Protein Solutions: Empowering ADC Drug Development
The CDH6 target is in a critical period of rapid development. The perfect combination of its unique biological characteristics and ADC technology has brought new therapeutic hope to patients with refractory tumors, and it is expected to play an important role in the field of oncology in the future. As an important partner in the field of biopharmaceutical R&D, KACTUS has meticulously created a series of high-quality recombinant CDH6 protein products, including recombinant CDH6 proteins and domain proteins targeting EC2, EC3, EC4, EC5, and combinatorial domains. These provide key reagent support for the development of CDH6 drugs targeting different domains (such as related projects by Daiichi Sankyo). 
Immobilized Anti-CDH6 antibody, hFc Tag at 5μg/ml (100μl/well) on the plate. Dose response curve for Human CDH6, His Tag with the EC50 of 1.85μg/ml determined by ELISA (QC Test).
Immobilized Human CDH6, hFc Tag at 1μg/ml (100μl/well) on the hFc Antibody precoated plate (2μg/ml). Dose response curve for Biotinylated Anti-CDH6 Antibody, hFc Avi Tag with the EC50 of 94.0ng/ml determined by ELISA. (QC Test).
Immobilized Biotinylated Human CDH6, His-Avi Tag at 5μg/ml (100μl/well) on the streptavidin precoated plate (5μg/ml). Dose response curve for Anti-CDH6 Antibody, Rabbit IgG Tag with the EC50 of 0.12μg/ml determined by ELISA (QC Test).
Immobilized Anti-CDH6 Antibody, hFc Tag at 5μg/ml (100μl/well) on the plate. Dose response curve for Human CDH6 (EC5del), His Tag with the EC50 of 37.7ng/ml determined by ELISA. (QC Test)
Product List
| Catalog Number |
Product Name |
| Human CDH6/Cadherin 6 Protein, His Tag | |
| Human CDH6/Cadherin 6 Protein, His Tag | |
| Human CDH6/Cadherin 6 Protein, Ultra Low Endotoxin, His Tag | |
| Human CDH6/Cadherin 6 Protein, hFc-Tag (IgG1) | |
| Biotinylated Human CDH6/Cadherin 6 Protein, His-Avi Tag | |
| Human CDH6/Cadherin 6(EC2del), His Tag | |
| Human CDH6/Cadherin 6 (EC3del) Protein, His Tag | |
| Human CDH6/Cadherin 6 (EC4del) Protein, His Tag | |
| Human CDH6/Cadherin 6 (EC5del) Protein, His Tag | |
| Human CDH6/Cadherin 6 EC3 Domain Protein, His Tag | |
| Mouse CDH6/Cadherin 6 Protein, His Tag | |
| Cynomolgus CDH6/Cadherin 6 Protein, His Tag | |
| Cynomolgus CDH6/Cadherin 6 Protein, Ultra Low Endotoxin, His Tag | |
| Human CDH6 (EC1del) Protein, His tag | |
| CDH-HM1E5 | Human CDH6 EC5 Domain, His Tag |
References
1. Stewart DB, Barth AI, Nelson WJ. Differential regulation of endogenous cadherin expression in Madin-Darby canine kidney cells by cell-cell adhesion and activation of beta-catenin signaling. J Biol Chem. 2000 Jul 7;275(27):20707-16.
2. Basu R, Taylor MR, Williams ME. The classic cadherins in synaptic specificity. Cell Adh Migr. 2015;9(3):193-201.
3. Bialucha CU, Collins SD, Li X, Saxena P, Zhang X, Dürr C, Lafont B, Prieur P, Shim Y, Mosher R, Lee D, Ostrom L, Hu T, Bilic S, Rajlic IL, Capka V, Jiang W, Wagner JP, Elliott G, Veloso A, Piel JC, Flaherty MM, Mansfield KG, Meseck EK, Rubic-Schneider T, London AS, Tschantz WR, Kurz M, Nguyen D, Bourret A, Meyer MJ, Faris JE, Janatpour MJ, Chan VW, Yoder NC, Catcott KC, McShea MA, Sun X, Gao H, Williams J, Hofmann F, Engelman JA, Ettenberg SA, Sellers WR, Lees E. Discovery and Optimization of HKT288, a Cadherin-6-Targeting ADC for the Treatment of Ovarian and Renal Cancers. Cancer Discov. 2017 Sep;7(9):1030-1045.
4. Bartolomé RA, Robles J, Martin-Regalado Á, Pintado-Berninches L, Burdiel M, Jaén M, Aizpurúa C, Imbaud JI, Casal JI. CDH6-activated αIIbβ3 crosstalks with α2β1 to trigger cellular adhesion and invasion in metastatic ovarian and renal cancers. Mol Oncol. 2021 Jul;15(7):1849-1865.
5. Suzuki H, Nagase S, Saito C, Takatsuka A, Nagata M, Honda K, Kaneda Y, Nishiya Y, Honda T, Ishizaka T, Nakamura K, Nakada T, Abe Y, Agatsuma T. Raludotatug Deruxtecan, a CDH6-Targeting Antibody-Drug Conjugate with a DNA Topoisomerase I Inhibitor DXd, Is Efficacious in Human Ovarian and Kidney Cancer Models. Mol Cancer Ther. 2024 Mar 4;23(3):257-271.
6. Lu W, Shi J, Zhang W, Covino N, Penticoff A, Phillips R, Cogswell J, Tatalick L, Pasas-Farmer S, Zhang J, Chen C, Wang Y, Shi H, Liu S, Meng X, Slosberg E. CUSP06, a Novel CDH6-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Multiple CDH6-Expressing Human Cancer Models. Pharmaceutics. 2025 Aug 13;17(8):1049.
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