TYMS and urinary bladder cancer: Indeed, pemetrexed and its polyglutamates are potent, tight-binding inhibitors of folate-dependent enzymes, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT) and show activity against a wide variety of solid tumours, including bladder cancer (Calvert, 2004).