In the present study, we showed that while the effect of Akt inhibition seems to be only modest in cancer cells overexpressing FGFR1, targeting FGFR1 in combination with Akti or PI3K-mTORi resulted in a strong and synergistic growth inhibition and induction of apoptosis in FGFR1-overexpressing EGFR-TKI-resistant NSCLC cells. Here, PIK3CA is linked to non-small cell lung carcinoma.