Camptothecins in Cancer Therapy [Paperback]

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.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.Part I: Biochemistry, Pharmacology, and ChemistryMechanism of Action of Topoisomerase 1 PoisonsLeroy F. Liu and Shyamal D. DesaiCrystallographic Insight Into the Mechanism of Drug-Induced Topoisomerase I DNA DamageAlex B. Burgin, Jr., Michael D. Feese, Bart L. Staker, and Lance StewartInhibitors of Topoisomerase I FunctionSidney M. HechtCytotoxic Mechanisms of the Topoisomerase 1 InhibitorsYves G. Pommier, Juana Barcel?, Takahisa Furuta, Haruyuki Takemura, Olivier Sordet, and ZhiYong LiaoBiochemical and Genetic Analyses of DNA Topoisomerase 1-Mediated DNA DamageRobert C. A. M. van Waardenburg and Mary-Ann BjornstiPreclinical Models for Evaluating Topoisomerase I-Targeted lÓR