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This collection of cutting-edge reviews comprehensively examines the current status of novel antifolates, an important class of anticancer drugs. The distinguished contributors discuss the preclinical and clinical pharmacology of methotrexate, other dihydrofolate reductase inhibitors, 5-fluorouracil, and the new generation of antifolates-the thymidylate synthase and glycinamide ribonucleotide formyltransferase inhibitors. In addition, they review in depth the modulation of antifolate drugs, folate and antifolate transport mechanisms, polyglutamation, resistance, and drug combinations, as well as pharmacogenomics, pharmacodynamics, regulation of gene expression, and mechanisms of cell death. Antifolate Drugs in Cancer Therapy provides entré to exciting new avenues for future research and constitutes a new standard reference for all basic scientists and clinicians engaged in cancer therapeutics.§