MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib

► PC9/gef cells are 270-fold resistant than PC9 cells to gefitinib. ► PC9/gef cells contain EGFR del 19 mutation but not EGFR T790M or MET amplification. ► NRAS Q61K mutation is found in all PC9/gef cells. ► ERK phosphorylation can not be suppressed by gefitinib in PC9/gef cells. ► MEK inhibitors plus gefitinib inhibit growth of PC9/gef cells in vitro and in vivo.