Computational Simulations of Aptamers Targeting
Epithelial Cell Adhesion Molecule (EpCAM)+ Breast
Cancer Cells

Abstract

Breast cancer remains the most prevalent cancer among women, with an incidence of over 2.3 million new cases in the United States. The epithelial cell adhesion molecule (EpCAM) receptor is highly expressed on the surface of breast cancer cells, where it plays a pivotal role in tumor progression and metastasis. Since the EpCAM receptor gets overexpressed on the surface of the breast cancer cells, they are an attractive target for both diagnosis and therapeutic application in breast cancer management. Aptamers are synthetic nucleic acids that selectively and with high affinity bind to the target molecules. We hypothesize that selected DNA-based aptamers can bind to the extracellular domain of EpCAM and serve as candidates for targeted breast cancer diagnostics. The structure of the EpCAM receptor was predicted using the AlphaFold 3 software, which provides insights into its function and structure. The aptamer 3D structure modeling was performed using the Vfold2D and Vfold3D software, respectively. In the next step, the aptamers were docked on the EpCAM receptor using the HDOCK2.0 software to obtain the EpCAM-aptamer complex output structures. These output structures were further validated using the binding energy calculations, and several interactions were formed between the EpCAM and aptamer. Based on these analyses, aptamer AS1411was selected as the most appropriate candidate for EpCAM-mediated breast cancer cell detection. This work advances the potential of EpCAM-targeted aptamers as targeted therapeutic and diagnostic agents against breast cancer.