CDH6 (Cadherin-6)

Class

CDH6-directed antibody-drug conjugate (topoisomerase I inhibitor payload, DXd)

Pathway

ADC internalization and payload-mediated DNA damage in CDH6-expressing tumor cells

Cadherin-6 (CDH6) is a calcium-dependent cell-adhesion protein normally expressed during kidney development and in the epithelium of certain organs, with expression largely restricted in healthy adult tissue. In several cancers, notably kidney and ovarian tumors, CDH6 is markedly overexpressed on the tumor cell surface, making it a candidate 'address label' for targeted therapy even though it plays no direct causal role in tumor growth. This mechanism exploits that expression pattern through an antibody-drug conjugate (ADC): a monoclonal antibody recognizes CDH6, is taken up (internalized) by the tumor cell, and releases a cytotoxic payload, in this case a topoisomerase I inhibitor known as DXd, once inside. Topoisomerase I inhibitors block an enzyme required for DNA to unwind during replication, causing DNA strand breaks and cell death in dividing cells. The rationale for coupling this payload to a CDH6-targeting antibody is to concentrate potent DNA-damaging chemotherapy specifically in tumor cells that display the target, sparing tissues that lack it. This approach is broadly relevant to solid tumors with high, relatively tumor-selective surface antigen expression, where conventional chemotherapy would cause substantial harm to healthy tissue and where more selective delivery could widen the window between anti-tumor effect and toxicity.