New Approaches to Cancer Chemotherapy with Methotrexate

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Abstract
THE folic acid antagonists were shown to have antileukemic activity by Farber and his colleagues in 1948.1 Since then the prototypical folic acid antagonist, methotrexate, has been found effective in a number of neoplastic diseases, including choriocarcinoma, head-and-neck cancer and breast cancer. Methotrexate inhibits the enzyme, dihydrofolate reductase, and thus diminishes reduced folate pools, which are essential cofactors, particularly for DNA synthesis, but also for purine and protein synthesis. Citrovorum factor (5-formyl tetrahydrofolate) supplies the product of the inhibited enzyme and thus can prevent, and when employed appropriately can rescue cells from, adverse biologic effects in in vitro and in . . .