Cadherin-6 (CDH6) (CDH6)

Cadherin-6 (CDH6), also known as K-cadherin, is a type II classical cadherin and a member of the cadherin superfamily of calcium-dependent cell adhesion molecules [1, 4]. It is a single-pass transmembrane glycoprotein that mediates homophilic cell-cell adhesion, which is essential for tissue integrity, morphogenesis, and embryonic development, particularly in the kidney and central nervous system [2, 6, 11]. In adult tissues, CDH6 expression is generally low and restricted to specific sites like renal tubules and bile ducts [4, 6]. However, CDH6 is significantly overexpressed in several malignancies, most notably serous ovarian cancer and renal cell carcinoma, where it is associated with tumor invasion, epithelial-mesenchymal transition (EMT), and poor prognosis [2, 7, 14]. As a therapeutic target, CDH6 is primarily addressed using antibody-drug conjugates (ADCs) like raludotatug deruxtecan (R-DXd) [2, 10]. These drugs utilize a humanized anti-CDH6 antibody to deliver a potent cytotoxic payload, such as the topoisomerase I inhibitor DXd, directly to cancer cells [3, 15]. Upon binding and internalization, the payload is released to induce DNA damage and apoptosis, while also exerting a bystander effect on neighboring tumor cells [2, 15]. Clinical development of CDH6-targeted therapies is currently focused on platinum-resistant ovarian cancer and advanced renal cell carcinoma, with safety profiles characterized by manageable gastrointestinal and hematologic toxicities, as well as a risk of interstitial lung disease [17, 19].

Other names

K-cadherinFetal kidney cadherinCAD6KCAD

Antibody-drug conjugate (ADC) targeting CDH6 to deliver a cytotoxic topoisomerase I inhibitor payload, leading to DNA damage and apoptosis.