Topoisomerases and Cancer
Topoisomerases are essential enzymes that regulate DNA supercoiling in cells and remove tangles and knots from the genome. However, because they generate DNA strand breaks as requisite intermediates in their catalytic reactions, they also have the capacity to fragment the genome. This potentially lethal feature of topoisomerases I, IIα, and IIβ has been exploited to treat a variety of human cancers. Anticancer drugs that target these enzymes kill cells by a unique mechanism. Rather than depriving cells of the essential functions of topoisomerases, these agents “poison” the enzymes and convert them to potent cellular toxins. Thus, they are called topoisomerase poisons to distinguish them from classic catalytic inhibitors. Topoisomerase I-targeted drugs represent an emerging class of anticancer agents, while topoisomerase II-targeted drugs include some of the most widely prescribed chemotherapeutics currently in clinical use. Together, these drugs are used to treat a variety of...
KeywordsAcute Myeloid Leukemia Lactone Ring Cleavage Complex Camptotheca Acuminata Catalytic Inhibitor
- Beretta GL, Zuco V, Perego P, Zaffaroni N (2012) Targeting DNA topoisomerase I with non-camptothecin poisons. Curr Med Chem 19:1238–1257Google Scholar