DNA Topoisomerases in Cancer Therapy: Present and Future [Hardcover]

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.

1 Reflections on an accidental discovery.- 2 Mechanisms of topoisomerase I inhibition by anticancer drugs.- 3 Mechanism of action of topoisomerase II-targeted anticancer drugs.- 4 Degradation of topoisomerase cleavable complexes.- 5 Yeast as a model system in the analysis of DNA topoisomerase I poisons.- 6 Understanding the action of drugs targeting TOP2: Yeast based systems for unraveling drug mechanisms.- 7 Cellular resistance to DNA topoisomerase I-targeting drugs.- 8 Development of new topoisomerase I-targeting compounds as candidate anticancer drugs.- 9 Development of new topoisomerase II-targeting compounds as candidate anticancer drugs.Commemorates the 30th anniversary of the discovery in 1971 of the first DNA topoisomerases, i.e topoisomerase I in E. coli Pioneer Jim Wang at Harvard University, contributed an article: `Reflections on an accidental discovery' of the enzyme