In Antifolate Drugs in Cancer Therapy, Ann Jackman and a panel of highly regarded researchers comprehensively review 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.

The wide and progressive scope of 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.

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Inhalt

Antifolate Drugs: Past and Future Perspectives, Robert C. Jackson. Folate Biochemistry and Nutrition in Relation to Antifolate Selectivity, Roy L. Kisliuk. Clinical Pharmacology and Resistance to Dihydrofolate Reductase Inhibitors, Richard Gorlick and Joseph R. Bertino. Development of Nonpolyglutamatable Dihydrofolate Reductase (DHFR) Inhibitors, Andre Rosowsky. Fluoropyrimidines as Antifolate Drugs, G.J. Peters and C.H. Köhne. Raltitrexed (Tomudex(TM)), a Highly Polyglutamatable Antifolate Thymidylate Synthase Inhibitor: Design and Preclinical Activity, Leslie R. Hughes, Trevor C. Stephens, F. Thomas Boyle, and Ann L. Jackman. Tomudex: Clinical Development, Philip Beale and Stephen Clarke. Preclinical Pharmacology Studies and the Clinical Development of a Novel Multitargeted Antifolate, MTA (LY231514), Chuan Shih and Donald E. Thronton. GW1843: A Potent, Non-competitive Thymidylate Synthase Inhibitor- Preclinical and Preliminary Clinical Studies, Gary K. Smith, Joseph W. Bigley, Inderjit K. Dev, David S. Duch, Robert Ferone and William Pendergast. Preclinical and Clinical Studies with the Novel Thymidylate Synthase Inhibitor Nolatrexed Dihydrochloride (Thymitaq(TM), AG337), Andy Hughes and A. Hilary Calvert. ZD9331, F. Thomas Boyle, Trevor C. Stephens, S.D. Averbuch, and Ann L. Jackman. Preclinical and Clinical Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitors Lometrexol and LY309887., Laurane G. Mendelsohn, John F. Worzalla, and Jackie M. Walling. AG2034: A GARFT Inhibitor with Selective Cytotoxicity to Cells that Lack a G1 Checkpoint, Theodore J. Boritzki, Cathy Zhang, Chalotte A. Bartlett, and Robert C. Jackson. Receptor- and Carrier-Mediated Transport Systems for Folates and Antifolates: Exploitation for Folate-Based Chemotherapy and Immunotherapy, G. Jansen. Folates as Chemotherapeutic Modulators, Julio Barredo, Marlene A. Bunni, Raghunathan Kamasamudram, and David G. Priest. Antifolate Polyglutamation in Preclinical and ClinicalAntifolate Resistance, John J. McGuire. Antifolates in Combination Therapy,Stephen P. Ackland, Madhu Garg, and Rosemary Kimbell. Pharmacodynamic Measurements and Predictors of Thymidylate Synthase Inhibitors, David Farrugia and Patrick G. Johnston. Moleccular Regulation of Expression of Thymidylate Synthase, Edward Chu, Jingfang Ju and John C. Schmitz. The Role of Uracil Misincorporation in Thymineless Death, G. Wynne Aherne and Shereal Brown. Thymeineless Death, Peter J. Houghton. Genetic Determinants of Cell Death and Toxicity, D. Mark Pritchard and John A. Hickman. Index.