To investigate possible mechanisms of resistance to FGFR inhibition, we studied the lung cancer cell lines DMS114 and H1581….Cells were treated with BGJ398 alone or in combination with 20 nmol/L trametinib....In summary, treatment of H1581 cells with FGFR inhibitors triggers the outgrowth of a preexisting drug-resistant subpopulation of cells. The resistant subpopulation demonstrated high-level amplification of NRAS, RAS, and MAPK activation as well as resistance to FGFR inhibition.