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Antibody-Based Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The Human Epithelial Cell Adhesion Molecule (EpCAM) is a Type I transmembrane glycoprotein consisting of two epidermal growth factor-like domains, one cysteine-poor region, one transmembrane domain and one short cytoplasmic tail. In normal cells and tissues, EpCAM expression is limited and the glycoprotein is shielded by tight junctions which limit its accessibility. In contrast, in tumor cells EpCAM is expressed on the whole cell surface, and thus becomes more accessible for binding. It is one of the most frequently and strongly expressed tumor-associated antigens in a number of tumor types including ovarian, gastric, colon, pancreatic, prostate, lung, and endometrial carcinoma. In particular, EpCAM is expressed on the vast majority of the main epithelial cancers that cause malignant ascites.
Circulating Tumor Cells and Personalized Medicine
Published in II-Jin Kim, Cancer Genetics and Genomics for Personalized Medicine, 2017
Jin Sun Lee, Mark Jesus M. Magbanua, Marc R. Jabon, John W. Park
Immunologic methods, in particular, target cell surface proteins expressed by tumor cells of epithelial origin. For example, the epithelial cell adhesion molecule (EPCAM) is a surface marker widely used for enrichment. Positive selection using magnetic beads coated with anti-EPCAM antibodies (immunomagnetic beads) allows for the separation of CTCs from blood cells. The EPCAM antibodies bind to CTCs, and a magnet is then used to capture cells labeled with beads. It is important to note, however, that epithelial marker-dependent approaches may fail to enrich for tumor cells that have undergone EMT (epithelial-to-mesenchymal transition), which is usually accompanied by down-regulation of epithelial markers.8 A novel approach that does not utilize specific surface markers is the CAM (collagen adherence matrix) assay (e.g., Vita Cap™).9 In this method, CTCs adhere to a collagen matrix while blood cells are washed away. It is also possible to use an antibody specific to blood cell markers (e.g., CD45) for negative selection.10
Immunotherapy of peritoneal carcinomatosis
Published in Wim P. Ceelen, Edward A. Levine, Intraperitoneal Cancer Therapy, 2015
Michael A. Ströhlein, Markus M. Heiss
The human epithelial cell adhesion molecule (EpCAM, CD326) represents a membrane-embedded protein that mediates epithelium-specific cell-to-cell adhesion [13]. Investigations on the expression of EpCAM on normal human tissue showed that the protein could primarily be detected on epithelial tissue including pancreas, colon, lung, bile ducts, and breast, whereas EpCAM-negative tissue includes bone marrow, lymphocytes, endothelium, heart, ovary, muscle, and mesenchymal tissue [14,15]. The high frequency of its overexpression on epithelial tumors qualifies EpCAM as a smart target for anticancer therapy. High-level EpCAM expression was found in gastric cancer, colon cancer, prostate cancer, and lung cancer [16]. Treatment of head and neck cancer and breast cancer cell lines with EpCAM-specific antisense or siRNAs resulted in the partial or complete reduction of cell migration, proliferation and invasive capacity [17,18].
HOTAIR knockdown impairs metastasis of cervical cancer cells by down-regulating metastasis-related genes
Published in Journal of Obstetrics and Gynaecology, 2023
Lei Shi, Dehui Zhang, Huijuan Han, Liangyu Zhang, Sirui Li, Fang Yang, Caijun He
Epithelial cell adhesion molecule (EpCAM) is known to be strongly associated with poor clinical outcomes in cancer patients (Park et al. 2020). It is regarded as a pro-metastatic gene and the presence of circulating cancer cells expressing EpCAM in the blood of cancer patients is strongly associated with poor prognosis (de Wit et al. 2018). This gene is upregulated in many tumours, such as squamous cell carcinoma (Stoecklein et al.2006) and breast cancer (Osta et al.2004). The expression of EpCAM also was downregulated in the cervical cell lines after HOTAIR knockdown. Previously, downregulation of EpCAM was shown to suppress the proliferation of gastric cancer and arrest cell cycle of AGS and SGC7901 cells (Wenqi et al.2009). In addition, silencing of EpCAM with siRNA was found to efficiently inhibits the proliferation of MCF-7 and WERI-Rb1 cells (Subramanian et al.2015). These data are consistent with our results.
Efficacy of epi-1 modified epirubicin and curcumin encapsulated liposomes targeting-EpCAM in the inhibition of epithelial ovarian cancer cells
Published in Journal of Liposome Research, 2023
Yu-Jia Wang, Ling Tang, Xu-Hong Lu, Ji-Tao Liu, Yuan-Yuan Wang, Hong-Xia Geng, Xue-Tao Li, Quan An
Among these systems, liposomes are noticeable attractive drug delivery system that not only encapsulate hydrophilic and hydrophobic drugs, but also increase blood circulation time, thereby improving drug delivery efficiency in TME (Jung et al.2010, Xin et al.2021). Liposomes composed of phospholipids and cholesterol have unique properties, including improved drug stability, excellent biocompatibility, reduced drug toxicity, and their tunable surface modifications, which offer many advantages over other drug carriers (Zununi Vahed et al.2017). Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that is expressed exclusively in epithelial cells and epithelial-derived tumors and was found to be overexpressed on cancer cells isolated from patients with EOC by immunohistochemical studies (Zheng et al.2017). EpCAM has been found to be involved in cell proliferation, migration, invasion, and differentiation and plays an important role in cancer metastasis, suggesting that it could be a molecular therapeutic target for EOC (Muynck et al.2020). Epi-1 (D-WRPTRURLLPWWICGSGSK) is a macrocyclic peptide with high affinity and specific binding to EpCAM, and modification on the surface of lipid nanoparticles can enhance active drug targeting and improve cellular uptake of drugs (Iwasaki et al.2015, Sakurai et al.2017).
CAR-T cell therapy for triple-negative breast cancer and other solid tumors: preclinical and clinical progress
Published in Expert Opinion on Investigational Drugs, 2022
Chiara Corti, Konstantinos Venetis, Elham Sajjadi, Lorenzo Zattoni, Giuseppe Curigliano, Nicola Fusco
Epithelial cell adhesion molecule (EpCAM) is a cell surface molecule involved in cell-to-cell adhesion and it is known to be highly expressed in colon and other epithelial carcinomas [71]. Recently, a real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to quantify the level of EpCAM mRNA expression in normal breast tissue as well as primary and metastatic BCs. EpCAM resulted overexpressed 100- to 1000-fold in primary and metastatic BC. Moreover, silencing of EpCAM gene expression with short interfering RNA (siRNA) resulted in a 35–80% decrease in the rate of cell proliferation in four different BC cell lines [71]. EpCAM siRNA treatment was associated with decreased cell migration (~91.8%) and reduced cell invasion (~96.4%) in BC MDA-MB-231 cell line [71]. Such results provide a rationale for exploiting EpCAM as a target for BC. In this regard, a phase I clinical trial is currently investigating third-generation EpCAM-CAR-T cells for the treatment of breast cancer (NCT02915445).