They are thymidylate synthase (TS) inhibitors: interrupting the action of this enzyme blocks the synthesis of pyrimidine thymidylate (dTMP), which is a nucleotide required for DNA replication Randomized trials have demonstrated local control and survival advantages using systemic 5-FU and radiation compared with radiation alone in patients with rectal cancer, esophageal cancer, and pancreatic cancer [150]. This evidence concerns the gene TYMS and familial pancreatic carcinoma.