Culprit and victim -- DNA topoisomerase II.

ABSTRACT

The phylogenetic antiquity of DNA topoisomerases indicates their vital function. Structure and maintenance of genomic DNA depend on the activity of these enzymes, and without them DNA replication and cell division are impossible. Topoisomerase II alpha has therefore become the main target of many antitumour therapy regimens, even though the exact mechanism of cell killing remains elusive. The success of this approach is limited by the development of spontaneous resistance, and drug-induced DNA damage can increase malignancy. Nevertheless, the combined use of topoisomerase-inhibiting drugs with different mechanisms of action promises to improve particular treatment designs. The degree of topoisomerase II expression in tumours may predict the clinical course and responsiveness to therapy.