Cadherin-6 (CDH6)

Class

CDH6-directed antibody-drug conjugate (topoisomerase I inhibitor payload, CPT116)

Pathway

Antibody-mediated delivery of a camptothecin-derivative topoisomerase I inhibitor causing DNA damage/apoptosis

Cadherin-6 (CDH6) is a calcium-dependent cell-adhesion protein normally expressed in kidney tissue during development and in the adult nephron, but it becomes markedly overexpressed on the surface of certain solid tumors, most notably renal cell carcinoma and some ovarian cancers. Because this overexpression is relatively tumor-selective, CDH6 serves as a homing beacon rather than a driver that needs to be blocked functionally. This mechanism exploits that property through an antibody-drug conjugate (ADC): a monoclonal antibody recognizes CDH6 on the tumor cell surface, is taken into the cell, and releases a potent cytotoxic payload, a camptothecin-derivative topoisomerase I inhibitor, directly inside the cancer cell. Topoisomerase I inhibitors interfere with an enzyme required for normal DNA unwinding during replication, and their action causes DNA strand breaks that trigger cell death. The rationale for this delivery strategy is to concentrate a potent chemotherapy-like agent specifically in CDH6-expressing tumor cells while sparing much of the systemic tissue that would be affected if the same payload were given as a conventional drug. This general approach—targeted delivery of DNA-damaging chemotherapy via a tumor-surface antigen—is broadly relevant to cancers where a distinguishing surface marker exists but no targetable driver mutation or pathway is available.