Camptothecins in Cancer Therapy (Cancer Drug Discovery and Development)

Clinical interest in the camptothecins continues to expand even though this class of topoisomerase I inhibitors has been studied for almost 50 years, and two early generation members of the family have gained FDA approval. 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. 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. Authoritative and up-to-date, Camptothecins in Cancer Therapy provides a comprehensive summary of camptothecin research, as well as a much-needed guide to all the latest information on their optimal therapeutic applications. 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. Front Matter....Pages i-xiii Front Matter....Pages 1-1 Mechanism of Action of Topoisomerase 1 Poisons....Pages 3-21 Crystallographic Insight Into the Mechanism of Drug-Induced Topoisomerase I DNA Damage....Pages 23-38 Inhibitors of Topoisomerase I Function....Pages 39-59 Cytotoxic Mechanisms of Topoisomerase 1 Inhibitors....Pages 61-107 Biochemical and Genetic Analyses of DNA Topoisomerase 1-Mediated DNA Damage....Pages 109-125 Preclinical Models for Evaluating Topoisomerase I-Targeted Drugs....Pages 127-151 Mechanisms of Resistance to Camptothecins....Pages 153-169 Recent Advances in Camptothecin Drug Design and Delivery Strategies....Pages 171-190 Front Matter....Pages 191-191 Clinical Experience With 9-Aminocamptothecin....Pages 193-206 Clinical Studies of Rubitecan (9-Nitro 20(S) Camptothecin)....Pages 207-228 Irinotecan....Pages 229-262 Clinical Experience With Topotecan....Pages 263-299 The Clinical Development of Lurtotecan....Pages 301-316 Preclinical and Clinical Development of Exatecan (DX-951f)....Pages 317-341 Camptothecins in the Treatment of Primary Brain Tumors....Pages 343-367 Camptothecins in the Treatment of Lung Cancer....Pages 369-419 Use of Camptothecins in the Treatment of Leukemia and Related Disorders....Pages 421-450 Back Matter....Pages 451-460 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. 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." --Résumé de l'éditeur "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