TYMS and lung carcinoma: High levels of thymidylate synthase expression lead to pemetrexed resistance in lung cancer.15,16 Knockdown of thymidylate synthase reverses the resistance of pemetrexed.15,16 We found that GMI inhibited the expression of thymidylate synthase in parental A549 and A549/A400 cells (Supplementary Fig. S2A).