In the study, we detect the combined anti-cancer effects and mechanisms between the BYL719 and the gefitinib, in various of EGFR mutated NSCLC cells with PI3K/AKT pathway activation in vitro and in vivo. The models of three-dimensional (3D) spheroid and the patient-derived lung cancer organoids are also chosen to confirm these findings for the better recapitulation of in vivo morphologies [18, 19]. The gene discussed is PIK3CA; the disease is lung cancer.