TYMS and non-small cell lung carcinoma: PEM inhibits several multiple folate-dependent enzymes, including thymidylate synthase (TS), and in non-small cell lung cancer PEM had a lower antitumor activity in squamous when compared to non-squamous histotypes [7–9] and this differential activity has been associated to higher levels of intracellular TS in squamous histology [6, 17].