BPS2026 – Investigating amivantamab-induced EGFR internalization and degradation in EGFR-mutant NSCLC

Amivantamab is an EGFR-MET bispecific antibody approved for EGFR exon 20 insertion mutant non-small cell lung cancer (NSCLC). While its clinical efficacy has been established, the intracellular trafficking route of amivantamab after receptor binding is not fully characterized in other EGFR-mutant NSCLC models, such as PC9 and H1975 cells. EGFR internalization and trafficking to recycling or degradative pathways play an essential role in regulating receptor signaling, how long the drug remains effective, and development of therapeutic resistance. Understanding the balance between recycling and degradation is essential for elucidating its therapeutic mechanism of amivantamab and predicting treatment outcomes. Here, we investigated the internalization and endocytic fate of amivantamab in EGFR-mutant NSCLC cell models. We used fluorescence microscopy approaches to visualize and track the internalization of fluorescently labeled amivantamab over time and assess its distribution across key endocytic compartments. Co-staining with markers of early endosomes, recycling endosomes, and lysosomes allow us to determine the relative contribution of each trafficking route. These experiments will offer a time-resolved view of amivantamab movement from the cell surface through endocytic compartments and ultimately toward receptor degradation or recycling. This project will provide new insights into how amivantamab enters lung cancer cells and where it goes inside the cell. A better understanding about these processes may clarify how amivantamab reduces EGFR signaling and guide strategies to optimize antibody-based this treatment work better and overcome drug resistance in NSCLC.