Camptothecins in Cancer Therapy

A critical review of our understanding of camptothecins, their shortcomings, and of the possibilities for improving their clinical performance. This work also discusses camptothecin analog development, drug delivery issues for optimizing their anticancer activity, and their potential use in a variety of different cancers.

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 potential of camptothecins, and the question of camptothecin resistance.

Part I: Biochemistry, Pharmacology, and Chemistry
Mechanism of Action of Topoisomerase 1 Poisons
Leroy F. Liu and Shyamal D. Desai
Crystallographic Insight Into the Mechanism of Drug-Induced Topoisomerase I DNA Damage
Alex B. Burgin, Jr., Michael D. Feese, Bart L. Staker, and Lance Stewart
Inhibitors of Topoisomerase I Function
Sidney M. Hecht
Cytotoxic Mechanisms of the Topoisomerase 1 Inhibitors
Yves G. Pommier, Juana Barcelo, Takahisa Furuta, Haruyuki Takemura, Olivier Sordet, and ZhiYong Liao
Biochemical and Genetic Analyses of DNA Topoisomerase 1-Mediated DNA Damage
Robert C. A. M. van Waardenburg and Mary-Ann Bjornsti
Preclinical Models for Evaluating Topoisomerase I-Targeted Drugs
Aarti S. Juvekar, Joyce Thompson, Clinton F. Stewart, and Peter J. Houghton
Mechanisms of Resistance to Camptothecins
Zeshaan A. Rasheed and Eric H. Rubin
Recent Advances in Camptothecin Drug Design and Delivery Strategies
Thomas G. Burke, Tian-Xiang Xiang, Bradley D. Anderson, and Lori J. Latus
Part II: Clinical Perspectives
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, James P. Stevenson, Christopher J. Twelves, and Peter J. O'Dwyer
Preclinical and Clinical Development of Exatecan (DX-8951f): 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, Missak Haigentz, Jr., Jorge Gomez, and Roman Perez-Soler
Use of Camptothecins in the Treatment of Leukemia and Related Disorders
Benjamin M. F. Mow and Scott H. Kaufmann
Index