Joseph R. Bertino, MD

The excellent review by Drs. Takimoto and Allegra summarizes the current status of the new antifolates in clinical development. Based on knowledge of why methotrexate is ineffective in the treatment of many tumors (ie, either intrinsic or acquired resistance), and on the identification of new targets for folate inhibitors (eg, thymidylate synthase [TS] and glycinamide ribonucleotide [GAR] transformylase), new antifolate development has recently received a great deal of attention from both industry and academic centers.