Molecular dynamics simulation-guided drug sensitivity prediction for lung cancer with rare <i>EGFR</i> mutations

Abstract

Significance A variety of rare mutations account for 10–20% of EGFR mutations in nonsmall cell lung cancer. However, due to high diversity, proper medication for patients with such mutations is impossible in daily clinic. To appropriately treat lung cancer patients harboring such rare EGFR mutations, a robust prediction model to predict sensitivities of rare EGFR mutants to existing drugs is strongly needed. Using molecular dynamics simulation-based model, we successfully predicted diverse sensitivities of EGFR exon 20 insertion mutants to existing inhibitors. The findings suggest the usefulness of in silico simulation to overcome mutation diversity at a clinically relevant level. The present in silico model will help in selecting effective drugs for these patients.