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TitleAntifolate Drugs in Cancer Therapy [electronic resource] / edited by Ann L. Jackman
ImprintTotowa, NJ : Humana Press : Imprint: Humana Press, 1999
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Descript X, 456 p. online resource


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 entrรฉ to exciting new avenues for future research, and constitutes a new standard reference for all basic scientists and clinicians engaged in cancer therapeutics


1 Antifolate Drugs: Past and Future Perspectives -- 2 Folate Biochemistry in Relation to Antifolate Selectivity -- 3 Clinical Pharmacology and Resistance to Dihydrofolate Reductase Inhibitors -- 4 Development of Nonpolyglutamatable DHFR Inhibitors -- 5 Fluoropyrimidines as Antifolate Drugs -- 6 Raltitrexed (Tomudextm), a Highly Polyglutamatable Antifolate Thymidylate Synthase Inhibitor: Design and Preclinical Activity -- 7 Tomudex: Clinical Development -- 8 Preclinical Pharmacology Studies and the Clinical Development of a Novel Multitargeted Antifolate, MTA (LY231514) -- 9 GW1843: A Potent, Noncompetitive Thymidylate Synthase Inhibitorโ{128}{148}Preclinical and Preliminary Clinical Studies -- 10 Preclinical and Clinical Studies with the Novel Thymidylate Synthase Inhibitor Nolatrexed Dihydrochloride (Thymitaqtm, AG337) -- 11 ZD9331: Preclinical and Clinical Studies -- 12 Preclinical and Clinical Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitors Lometrexol and LY309887 -- 13 AG2034: A GARFT Inhibitor with Selective Cytotoxicity to Cells that Lack a G1 Checkpoint -- 14 Receptor- and Carrier-Mediated Transport Systems for Folates and Antifolates: Exploitation for Folate-Based Chemotherapy and Immunotherapy -- 15 Folates as Chemotherapeutic Modulators -- 16 Antifolate Polyglutamylation in Preclinical and Clinical Antifolate Resistance -- 17 Antifolates in Combination Therapy -- 18 Pharmacodynamic Measurements and Predictors of Response to Thymidylate Synthase Inhibitors -- 19 Molecular Regulation of Expression of Thymidylate Synthase -- 20 The Role of Uracil Misincorporation in Thymineless Death -- 21 Thymineless Death -- 22 Genetic Determinants of Cell Death and Toxicity

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