This study aimed to determine whether dual blockade of PI3K and IR/IGF-1R signaling could overcome this adaptive resistance.<h4>Methods</h4>We assessed the effects of combining ceritinib, an ALK and IR/IGF-1R inhibitor, with a PI3K/AKT inhibitor in PIK3CA E545K-mutant H460 NSCLC cells. Here, INSR is linked to non-small cell lung carcinoma.