epithelial cell adhesion molecule

Overview

Epithelial cell adhesion molecule (EpCAM), also known as CD326, is a cell-surface glycoprotein widely used as a marker of epithelial-derived cells and many epithelial tumors. In biomedical research, EpCAM is most often discussed as a tumor-associated target rather than as a classical adhesion receptor, because its expression is frequently increased in carcinomas and can be exploited for tumor detection, imaging, biomarker enrichment, and targeted therapy.

Biologically, EpCAM is relevant to cancer cell behavior, including tumor cell identification and the study of stemness-associated phenotypes. In recent research, EpCAM has been linked with epithelial tumors such as colorectal cancer, head and neck squamous cell carcinoma, and other EpCAM-positive malignancies. Its presence on tumor cells and tumor-derived extracellular vesicles has made it a useful target for liquid biopsy approaches, fluorescence-guided delineation, and engineered immunotherapies, including bispecific antibodies and CAR-T cells.

Focus of Latest Publications

Recent publications have focused on epithelial cell adhesion molecule (EpCAM/CD326) primarily as a tumor-associated target for detection, imaging, and selective delivery strategies. In head and neck squamous cell carcinoma, EpCAM was reported to be substantially overexpressed and was explored as a target for near-infrared fluorescent antibodies to improve microscopic delineation of primary and recurrent tumors during surgery. In a separate liquid-biopsy context, EpCAM was used to capture EpCAM-positive tumor-derived extracellular vesicles with molecularly imprinted polymers designed from the N-terminal EpCAM sequence, supporting selective enrichment of tumor EVs from complex biological samples.

Several studies extended EpCAM targeting to exosome and extracellular vesicle analysis. A microchip electrophoresis-assisted branched hybridization chain reaction assay used an EpCAM-recognizing aptamer to distinguish exosomes from different cancer cell types, reporting high EpCAM abundance on MCF-7-derived exosomes relative to those from A549 and HeLa cells. Another wash-free digital plasmonic droplet microfluidic platform included EpCAM among the EV surface markers targeted by antibody-functionalized gold nanoparticles, enabling rapid marker-specific profiling of tumor-derived EVs from small plasma volumes.

EpCAM has also been used as a tumor-selective anchor for immunotherapy design. A bispecific antibody, KK2269, was engineered to target EpCAM on tumor cells and CD40 on antigen-presenting cells, with the goal of activating APCs only in the presence of EpCAM-expressing tumors. In mouse tumor models, KK2269 showed antitumor activity in combination with several agents, including docetaxel, doxorubicin, oxaliplatin, and anti-PD-1 antibody, with docetaxel producing the strongest effect. The combination of docetaxel and KK2269 increased APC and T-cell activation markers and showed activity in both subcutaneous and intrahepatic transplantation models.

Across these reports, EpCAM was consistently treated as a marker of epithelial tumor cells and tumor-derived vesicles rather than as a mechanistic driver. The studies collectively emphasize its utility for fluorescence-guided surgery, selective EV capture for proteomic biomarker discovery, exosome discrimination, and tumor-targeted immune activation.

Key Publications

May Targeting EpCAM expression via near-infrared fluorescent antibodies enables microscopic delineation of primary and recurrent HNSCC. (BMC cancer, 2026, PMID 42178533): "Epithelial cell adhesion molecule (EpCAM/CD326) is substantially overexpressed in HNSCC representing a potential target for fluorescence-guided delineation of HNSCC."
May Selective Recognition of Tumor-Derived EVs by EpCAM-Imprinted Polymers for Proteomic Biomarker Discovery. (Analytical chemistry, 2026, PMID 42117374): "EpCAM, a key biomarker for epithelial tumors, is overexpressed in multiple cancers and enriched on tumor-derived extracellular vesicles (EVs), positioning it as a promising liquid biopsy target."
May Wash-Free Digital Detection of Tumor Extracellular Vesicles via Plasmonic Droplet Microfluidics. (ACS sensors, 2026, PMID 42011810): "Plasma (10 μL) is coencapsulated with Ab-AuNPs targeting CD9, EpCAM, PSA, PSMA, and PD-L1 in picoliter droplets."
Apr Docetaxel-Induced Immune Activation Shows Antitumor Synergy With the Tumor-Targeted CD40 Agonist KK2269. (Cancer science, 2026, PMID 41989931): "We developed KK2269, a bispecific antibody targeting epithelial cell adhesion molecule (EpCAM) on tumor cells and CD40 on APCs, designed to selectively activate APCs in the presence of EpCAM-positive tumors."
Feb Biofilm surface proximity-induced branched hybridization chain reaction strategy based on microchip electrophoresis for distinguishing exosomes from different cancer cells. (Talanta, 2026, PMID 41719909): "It uses an aptamer to identify the epithelial cell adhesion molecule (EpCAM) protein on the exosome surface by adjacent hybridization reaction on the biofilm surface."
Apr Alpha-fetoprotein acts as a key regulator of cancer stemness in hepatocellular carcinoma via PI3K/Akt pathway. (Cellular signalling, 2026, PMID 41651174): "Comparative analyses demonstrated that AFP ablation markedly reduced tumorigenic potential in vivo, accompanied by downregulation of stemness markers (EPCAM and CD44) and inhibition of PI3K/Akt signaling."