At the doses of methotrexate required for efficacy in cancer, it acts as a competitive inhibitor of dihydrofolate reductase (DHFR), hence it will reduce downstream intermediates of the folate pathway, and ultimately inhibit nucleotide synthesis, resulting in impaired DNA replication and repair.65–67 This mechanism for efficacy in cancer treatment results in arrest in the S phase of the cell cycle eventually leading to apoptosis. The gene discussed is DHFR; the disease is cancer.