TYMS and colorectal carcinoma: LV potentiates 5-FU cytotoxicity to CRC cells by promoting ternary complex formation involving (i) the active FP metabolite fluorodeoxyuridylate, (ii) the target enzyme thymidylate synthase (TS), and (iii) the reduced folate co-factor N5,N10-tetrahydrofolate, to irreversibly inhibit TS activity and de novo thymidylate biosynthesis (Figure 1B) [1].