In silico experiments showed that inhibition of both mTOR and PI3K can be synergistically effective in LKB1-deficient NSCLC. In vitro and in vivo experiments showed the synergistic effect of mTOR inhibition and PI3K inhibition in LKB1-mutant NSCLC cell lines. The sensitivity to dual inhibition of mTOR and PI3K is higher in LKB1-mutant cell lines than in wild-type cell lines....hen BKM-120 was combined with rapamycin, the differences in sensitivity between LKB1 wild-type and LKB1-mutant cell lines became significant, with mutant cell lines growing much more slowly than wild-type lines.