Camptothecins in Cancer Therapy (Cancer Drug Discovery and Development)

A critical review our current understanding of camptothecins, their shortcomings, and of the possibilities for improving their clinical performance. The authors discuss new camptothecin analog development, drug delivery issues for optimizing their anticancer activity, and their potential use in a variety of different cancers. Additional chapters describe what is known about the biochemistry, the pharmacology, and the chemistry of the camptothecins, including the mechanism of topoisomerase and how camptothecins poison this enzyme, the use of animal models in defining the anticancer potential of camptothecins, and the question of camptothecin resistance. Cover......Page 1 Camptothecins in Cancer Therapy......Page 2 Cancer Drug Discovery and Development Series......Page 3 Title Page......Page 4 Copyright Page......Page 5 Dedication......Page 6 Preface......Page 7 Contents......Page 8 Contributors......Page 10 Part I. Biochemistry,Pharmacology,and Chemistry......Page 13 1. Mechanism of Action of Topoisomerase 1 Poisons......Page 14 2. Crystallographic Insight Into the Mechanism of Drug-Induced Topoisomerase I DNA Damage......Page 33 3. Inhibitors of Topoisomerase I Function......Page 49 4. Cytotoxic Mechanisms of Topoisomerase 1 Inhibitors......Page 70 5. Biochemical and Genetic Analyses of DNA Topoisomerase 1-Mediated DNA Damage......Page 117 6. Preclinical Models for Evaluating Topoisomerase I-Targeted Drugs......Page 134 7. Mechanisms of Resistance to Camptothecins......Page 159 8. Recent Advances in Camptothecin Drug Design and Delivery Strategies......Page 176 Part II. Clinical Perspectives......Page 196 9. Clinical Experience With 9-Aminocamptothecin:Lessons for New Drug Development......Page 197 10. Clinical Studies of Rubitecan (9-Nitro 20(S)Camptothecin)......Page 211 11. Irinotecan:Current Clinical Status and Pharmacological Aspects......Page 233 12. Clinical Experience With Topotecan......Page 267 13. The Clinical Development of Lurtotecan:Experience With Water-Soluble and Liposomal Forms......Page 304 14. Preclinical and Clinical Development of Exatecan(DX-8951f):A Hexacyclic Camptothecin Analog......Page 320 15. Camptothecins in theTreatment of Primary Brain Tumors......Page 345 16. Camptothecins in the Treatment of Lung Cancer......Page 370 17. Use of Camptothecins in the Treatment of Leukemia and Related Disorders......Page 421 Index......Page 451 Mechanism of action of topoisomerase I poisons / Leroy F. Liu and Shyamal D. Desai Crystallographic insight into the mechanism of drug-induced topoisomerase I DNA damage / Alex B. Burgin, Jr., Bart L. Staker, and Lance Stewart Inhibitors of topoisomerase I function / Sidney M. Hecht Cytotoxic mechanisms of the topoisomerase I inhibitors / Yves Pommier ... [et al.] Biochemical and genetic analyses of DNA topoisomerase I-mediated DNA damage / Robert C.A.M. Van Waardenburg and Mary-Ann Bjornsti Preclinical models for evaluating topoisomerase-I targeted drugs / Aarti S. Juvekar ... [et al.] Mechanisms of resistance to camptothecins / Zeshaan A. Rasheed and Eric H. Rubin Recent advances in camptothecin drug design and delivery strategies / Thomas G. Burke ... [et al.] Clinical experience with 9-aminocamptothecin: lessons for new drug development / Chris H. Takimoto Clinical studies of rubitecan (9-nitro 20(s) camptothecin) / Hilary Hewes, Judith A. Smith, and Claire Verschraegen Irinotecan: current clinical status and pharmacological aspects / Laurent P. Rivory Clinical experience with topotecan / Aimee K. Bence and Val R. Adams The clinical development of lurtotecan: experience with water-soluble and liposomal forms / Keith T. Flaherty ... [et al.] Preclinical and clinical development of dx-8951f (exatecan mesylate): a hexacyclic camptothecin analog / Eric K. Rowinsky Camptothecins in the treatment of primary brain tumors / Clinton F. Stewart, Markos Leggas, and Henry S. Friedman Camptothecins in the treatment of lung cancer / Pankaj Kumar ... [et al.] Use of camptothecins in the treatment of leukemia and related disorders / Bejamin M.F. Mow and Scott H. Kaufmann. This is a critical review of our current understanding of camptothecins, their shortcomings, and of the possibilities for improving their clinical performance. The authors discuss new camptothecin analog development, drug delivery issues for optimizing their anticancer activity, and their potential use in a variety of different cancers. Additional chapters describe what is known about the biochemistry, the pharmacology, and the chemistry of the camptothecins, including the mechanism of topoisomerase and how camptothecins poison this enzyme, the use of animal models in defining the anticancer p "In Camptothecins in Cancer Therapy, leading clinicians and researchers critically review our current understanding of camptothecins, their shortcomings, and the possibilities for improving their clinical performance. The authors discuss new camptothecin analog development, drug delivery issues for optimizing their anticancer activity, and their potential use in a variety of different cancers."--BOOK JACKET