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Jordan VC
Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer
Br J Pharmacol. 2006 Jan;147 Suppl 1 :S269-76
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Abstract
Antihormonal therapy targeted to the oestrogen receptor (OER) is recognized as a significant advance in the treatment and prevention of breast cancer. However, the research method used to achieve the current successes seen in the clinic was not linear but was based on the changing fashions in research and the application of appropriate testing models. The discovery and investigation of nonsteroidal antioestrogens by the pharmaceutical industry during the 1960s was initially an exciting prospect for clinical development. The drugs were superb antifertility agents in laboratory animals, so the prospect of marketing a 'morning after' pill was a high priority. Unfortunately, the reproductive endocrinology of the rat was found to be completely different from that of the human. Antioestrogens, in fact, improved fertility by inducing ovulation in subfertile women so much of the drug development was discontinued. The successful reinvention of ICI46,474 from its origins as a failed contraceptive to a pioneering breast cancer treatment targeted to the OER presaged the development of the current menu of medicines targeted to a range of different survival mechanisms in cancer cells.
Notes
Jordan, V Craig 5P50CA89018-4/CA/United States NCI Historical Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review England British journal of pharmacology Br J Pharmacol. 2006 Jan;147 Suppl 1:S269-76.