Mathematical Modeling of the Dimerization of EGFR and ErbB3 in Lung Adenocarcinoma

The most common driver mutations in lung adenocarcinoma occur in the EGFR gene. Gefitinib, an EGFR tyrosine kinase inhibitor, is an effective therapy for lung adenocarcinoma with EGFR mutations. However, resistant tumors inevitably arise. One of the mechanisms conferring gefitinib resistance is the amplification of the MET gene, which is observed in 5–22% of all cases. A previous study suggested that MET overexpression may cause gefitinib resistance through ErbB3, and most likely through the formation of EGFR-ErbB3 heterodimers. In this study, we focused on the dimer formation of EGFR and ErbB3 in lung adenocarcinoma cells and built a mathematical model using ordinary differential equations. To simulate the dimerization process of EGFR and ErbB3, we determined the molecular concentrations of each on the cell surface by flow cytometry and estimated unknown reaction constants by dimensional analysis. Our mathematical model would provide a quantitative understanding of dimer formation, one which cannot be obtained by a molecular biology methods.