We investigated new approaches to enhance the efficacy of pemetrexed, and found that the combination of rapamycin and pemetrexed showed synergistic anti-proliferative effects in NSCLC cells and enhanced mTOR inhibition, as demonstrated by decreases in the phosphorylation of the downstream components of this pathway such as 4E-BP1. This evidence concerns the gene EIF4EBP1 and non-small cell lung carcinoma.