Cadherin-3 (P-cadherin) (CDH3)

Cadherin-3, commonly known as P-cadherin, is a calcium-dependent transmembrane protein that facilitates cell-cell adhesion and is vital for maintaining the structural integrity of various epithelial tissues (UniProt: P22223). It is primarily expressed in the basal layer of stratified epithelia, such as the skin and hair follicles, but is significantly overexpressed in several aggressive cancers, including triple-negative breast cancer, pancreatic cancer, and gastric adenocarcinoma (PubMed: 28630041). In these oncogenic contexts, P-cadherin promotes tumor progression by enhancing cell migration, invasion, and survival through the modulation of signaling pathways like Wnt/beta-catenin (PubMed: 25236391). The extracellular domain of P-cadherin is a prominent therapeutic target because it is accessible to circulating antibodies and exhibits a high tumor-to-normal tissue expression ratio in specific indications. Current drug development efforts focus on utilizing this domain for the delivery of cytotoxic agents via antibody-drug conjugates (ADCs) or for recruiting T-cells to tumor sites using bispecific antibodies (PubMed: 30104315). However, the presence of P-cadherin in normal skin and hair follicles presents a challenge for therapeutic window management, as on-target off-tumor effects can lead to dermatological toxicities (PubMed: 21170087).

Other names

P-cadherinPlacental cadherinCDHPCDH3

Antibody-drug conjugate (ADC) mediated cytotoxicity; Bispecific T-cell engager (BiTE) mediated immune response; Inhibition of cell-cell adhesion signaling.