In this study, we explored the mechanisms associated with resistance to PI3K/Akt/mTOR inhibitors in non-small cell lung cancer (NSCLC) cells that were resistant to the usual PI3K/mTOR inhibitor BEZ235, underscoring biochemical pathways and proposing new interventions that may pave the way to overcome resistance. Here, AKT1 is linked to non-small cell lung carcinoma.