TOPOISOMERASE-II-ALPHA AND TOPOISOMERASE-BETA AS THERAPY TARGETS IN BREAST-CANCER

Topoisomerase II enzymes play an essential role in human DNA metabolis m. They are also recognized as primary targets of a number of anti-can cer drugs used in the treatment of breast cancer, which remains a lead ing cause of cancer-related death in women. While topoisomerase inhibi tors have produced significant response rates in this disease, their u se has been limited both by toxicity and by the development of resista nce. In this article we review the extensive work which has not only i ncreased our understanding of the biochemistry and molecular biology o f type II topoisomerases but also enabled more rational drug design. S uch knowledge should translate into increased clinical efficacy in the treatment of breast cancer and other malignancies.