Anti-EGFR Aptamers as Targeted Therapeutic Agents for Non-Small Cell Lung Cancer (NSCLC)

Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer and is characterized by the rapid and uncontrolled reproduction of abnormal cells. Based on the receptor found on the cancer cell’s surface, NSCLC can be classified as either (a) wild-type Epidermal Growth Factor Receptor (EGFR) or (b) mutant EGFR (EGFRvIII). Aptamers are single-stranded nucleic acids that bind to specific targets, such as proteins like EGFR. Recently, aptamers targeting the EGFR cancer cells have been developed. We hypothesize that the aptamers used in this research should specifically bind to the EGFR receptor and bind minimally to its mutant EGFRvIII receptor. Therefore, a targeted therapy for NSCLC that focuses on EGFR can be developed. First, we employed the Vfold2D and Vfold3D webservers to construct 2-dimensional and 3-dimensional models of aptamers. Subsequently, we conducted molecular docking analysis to view the interactions between aptamers and the EGFR binding site. Finally, we used the PLIP software to collect data on receptor-aptamer interactions, including hydrophobic interactions, hydrogen bonds, cation interactions, and salt bridges. The results show that out of eight aptamers used in this research, five binds to the EGFR receptor, while only one binds to the EGFRvIII receptor. This shows the specificity of these aptamers to the EGFR receptor and that they could be used in the EGFR NSCLC. This research work will help us design novel aptamers that can be used in the EGFR NSCLC targeted therapy.

Keywords: Non-Small Cell Lung Cancer (NSCLC), EGFRvIII, Aptamer.