Pemetrexed has been reported to target thymidylate synthase, and study also reported that EGFR-TKI can down-regulate TS expression.13,14 La Monica et al. also reported that gefitinib combined with pemetrexed prevented the acquisition of TKI resistance in NSCLC cell lines carrying EGFR-activating mutation.15 The synergistic effect of TKI and pemetrexed has great promise in lung adenocarcinoma treatment. Here, EGFR is linked to lung adenocarcinoma.