Dual inhibitors of human DNA topoisomerase II and other cancer-related targets.

Abstract

Human DNA topoisomerase II is an important target in anticancer therapy. Despite the clinical success of drugs that target topoisomerase II, the development of resistant cancer cells can limit their clinical efficacy. To maximize the therapeutic potential of anticancer drugs, combination therapies and multi-target drugs have been suggested in many studies, where the use of multi-target drugs is advantageous from the pharmacokinetics point of view. There are various different options for the preparation of dual-target or multiple-target inhibitors, as topoisomerase II is both structurally (e.g., topoisomerase I, Hsp90, kinases) and functionally (e.g., histone deacetylases, proteasome) connected to many validated anticancer targets. In this article, we discuss the scientific background behind targeting topoisomerase II together with a number of other targets important in cancer therapy, we review the present status and discuss further options in the field.