Topoisomerases II alpha and beta as therapy targets in breast cancer.
Topoisomerase II enzymes play an essential role in human DNA metabolism. They are also recognized as primary targets of a number of anti-cancer drugs used in the treatment of breast cancer, which remains a leading cause of cancer-related death in women. While topoisomerase inhibitors have produced significant response rates in this disease, their use has been limited both by toxicity and by the development of resistance. In this article we review the extensive work which has not only increased our understanding of the biochemistry and molecular biology of type II topoisomerases but also enabled more rational drug design. Such knowledge should translate into increased clinical efficacy in the treatment of breast cancer and other malignancies.
Isaacs
R J
RJ
Imperial Cancer Research Fund, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, UK.
Davies
S L
SL
Wells
N J
NJ
Harris
A L
AL
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000502:physiology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D059005:Topoisomerase II Inhibitors
D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II