DHFR and malignant pleural mesothelioma: Pemetrexed, a multitarget antifolate, is effective in non-squamous NSCLC and malignant pleural mesothelioma, with the main focus on inhibition of enzymes involved in pyrimidine and purine synthesis such as thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT).