DNA Topoisomerases in Cancer Therapy Present and Future

This volume commemorates the 30th anniversary of the discovery in 1971 of the first DNA topoisomerases, i.e topoisomerase I in E. coli, then provisionally named `omega' protein, by the pioneering work of Jim Wang at Harvard University, who has contributed an article to this volume: `Reflections on an accidental discovery' of the enzyme. Many kinds of topoisomerase have since been found from type I through to type VI in a variety of organisms ranging from viruses to higher eukaryote mammals. The wide distribution of enzymes in various forms of life implies that the DNA topoisomerase is essential for life.

In the mid 80's type I and II enzymes were found to be the intracellular targets of a number of efficacious anticancer drugs such as doxorubicin, mitoxantrone, etoposide and camptothecin as a result of a continued efforts of many investigators, especially Leroy Liu and his collaborators at Johns Hopkins University. Readers will find a series of chapters written by researchers actively engaged in the expanding field of topoisomerase and their inhibitors. The series of chapters cover review articles on pharmacology and the molecular mechanism of topoisomerase I- and II-targeting anticancer drugs in mammals and in the yeast Saccharomyces cerevisiae, which has proved to be a superb model organism for studies of anticancer drugs. This volume compiles up-to-date information on the topoisomerase-targeting compounds in clinical and preclinical development as a useful and important reference book for students and researchers in the field of pharmacology, toxicology, oncology and molecular biology.