DHFR and cancer: For example, treatment of cancer with chemotherapy agent fluorouracil (5-FU), which is an inhibitor of thymidylate synthase, or with methotrexate, an inhibitor of dihydrofolate reductase and folates, leads to depletion of deoxyribonucleotides and perturbed DNA synthesis, which amounts a lethal level metabolic stress to cancer cells (Longley et al., 2003).