Cadherin-3 (CDH3) (CDH3)

Cadherin-3 (CDH3), also known as P-cadherin, is a calcium-dependent cell-cell adhesion glycoprotein belonging to the classical cadherin superfamily [UniProt P22223]. It plays a vital role in maintaining tissue architecture by mediating homotypic cell-cell interactions and modulating intracellular signaling pathways, including those involving Wnt and Rho GTPases [NCBI Gene 1001, PMID: 31434715]. While its physiological expression is primarily limited to the basal layer of stratified epithelia and hair follicles, CDH3 is significantly overexpressed in various solid tumors, such as triple-negative breast cancer and pancreatic cancer [PMID: 31434715]. This overexpression is linked to increased tumor cell motility, invasion, and the epithelial-mesenchymal transition (EMT), often serving as a marker for poor clinical prognosis [PMID: 28455364]. Consequently, CDH3 is a prominent therapeutic target for antibody-drug conjugates (ADCs) and bispecific antibodies, such as PF-06671008 and DS-6010a, which aim to selectively eliminate cancer cells while minimizing damage to normal tissues [PMID: 28455364, ClinicalTrials.gov NCT03243331]. However, the presence of CDH3 in normal skin and hair follicles presents a challenge for drug development, as on-target off-tumor effects can lead to dermatological toxicities [PMID: 28455364].

Other names

P-cadherinPlacental cadherinCDHPHJMDPCAD

Antibody-drug conjugate (ADC) mediated cytotoxicity and T-cell redirection via bispecific antibodies targeting the extracellular domain of the protein product.