Figure 6. Mechanisms of resistance to EGFR TKIs in PC9 cells.
Treatment of PC9 cells with reversible quinazoline-based TKIs (upper line) or clinical concentrations of irreversible TKI (middle line) leads to emergence of the EGFR T790M mutation as a mechanism of resistance. Treatment with a T790M -potent EGFR TKI (bottom line) prevents emergence of the EGFR T790M mutation and results in a sequential acquisition of non-T790M resistance mechanisms involving IGF1R and MAPK pathways.