Fluoropyrimidines are intracellularly converted into the antifolate 5-fluorodeoxyuridine monophosphate (5-FdUMP) that can form a covalent intermediate with the folate-dependent enzyme thymidylate synthase (TYMS)6 Consequently, the formation of dTMP from dUMP is inhibited which results in an imbalance of the nucleotide pool that affects DNA synthesis, possibly through incorporation of uracil, and impairs genome replication, with negative consequences for rapidly dividing cells such as cancer cells. Here, TYMS is linked to cancer.