TY - JOUR
T1 - Tamoxifen
T2 - Catalyst for the change to targeted therapy
AU - Jordan, V. Craig
N1 - Funding Information:
Dr. Jordan is supported by the Department of Defense Breast Program under Award Number BC050277 Center of Excellence (Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense), FCCC Core Grant NIH P30 CA006927, R01-1620905, The Alfred G. Knudson Endowed Chair in Cancer Research and the Weg Fund of Fox Chase Cancer Center.
Funding Information:
ICI, 46,474 was examined systematically in my laboratory to explore mechanisms and applications that could be exploited in the clinic. These studies were supported by ICI with unrestricted funds, first at the Worcester Foundation (1972–1974) and subsequently at the University of Leeds as a University Joint/Research Scheme (1974–1979). Most importantly, ICI arranged for thousands of rats to be chauffeured from Alderley Park to Leeds so I could complete my work. Those free rats, as it turned out, would be worth their weight in gold with the billions of pounds of profits earned with tamoxifen! Simultaneously, Rob Nicholson, at the Tenovus Institute in Cardiff started to use tamoxifen as a laboratory tool to investigate oestrogen and antioestrogen action in the DMBA-induced rat mammary tumour model. Again, these studies were published in the European Journal of Cancer. 26–28
PY - 2008/1
Y1 - 2008/1
N2 - In the early 1970s, a failed post-coital contraceptive, ICI 46,474, was reinvented as tamoxifen, the first targeted therapy for breast cancer. A cluster of papers published in the European Journal of Cancer described the idea of targeting tamoxifen to patients with oestrogen receptor positive tumours, and proposed the strategic value of using long-term tamoxifen therapy in an adjuvant setting with a consideration of the antitumour properties of the hydroxylated metabolites of tamoxifen. At the time, these laboratory results were slow to be embraced by the clinical community. Today, it is estimated that hundreds of thousands of breast cancer patients are alive today because of targeted long-term adjuvant tamoxifen therapy. Additionally, the first laboratory studies for the use of tamoxifen as a chemopreventive were published. Eventually, the worth of tamoxifen was tested as a chemopreventive and the drug is now known to have an excellent risk benefit ratio in high risk pre-menopausal women. Overall, the rigorous investigation of the pharmacology of tamoxifen facilitated tamoxifen's ubiquitous use for the targeted treatment of breast cancer, chemoprevention and pioneered the exploration of selective oestrogen receptor modulators (SERMs). This new concept subsequently heralded the development of raloxifene, a failed breast cancer drug, for the prevention of osteoporosis and breast cancer without the troublesome side-effect of endometrial cancer noted in post-menopausal women who take tamoxifen. Currently, the pharmaceutical industry is exploiting the SERM concept for all members of the nuclear receptor superfamily so that medicines can now be developed for diseases once thought impossible.
AB - In the early 1970s, a failed post-coital contraceptive, ICI 46,474, was reinvented as tamoxifen, the first targeted therapy for breast cancer. A cluster of papers published in the European Journal of Cancer described the idea of targeting tamoxifen to patients with oestrogen receptor positive tumours, and proposed the strategic value of using long-term tamoxifen therapy in an adjuvant setting with a consideration of the antitumour properties of the hydroxylated metabolites of tamoxifen. At the time, these laboratory results were slow to be embraced by the clinical community. Today, it is estimated that hundreds of thousands of breast cancer patients are alive today because of targeted long-term adjuvant tamoxifen therapy. Additionally, the first laboratory studies for the use of tamoxifen as a chemopreventive were published. Eventually, the worth of tamoxifen was tested as a chemopreventive and the drug is now known to have an excellent risk benefit ratio in high risk pre-menopausal women. Overall, the rigorous investigation of the pharmacology of tamoxifen facilitated tamoxifen's ubiquitous use for the targeted treatment of breast cancer, chemoprevention and pioneered the exploration of selective oestrogen receptor modulators (SERMs). This new concept subsequently heralded the development of raloxifene, a failed breast cancer drug, for the prevention of osteoporosis and breast cancer without the troublesome side-effect of endometrial cancer noted in post-menopausal women who take tamoxifen. Currently, the pharmaceutical industry is exploiting the SERM concept for all members of the nuclear receptor superfamily so that medicines can now be developed for diseases once thought impossible.
KW - Antioestrogen
KW - Breast cancer
KW - Chemoprevention
KW - Raloxifene
KW - Selective oestrogen receptor modulator
KW - Tamoxifen
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U2 - 10.1016/j.ejca.2007.11.002
DO - 10.1016/j.ejca.2007.11.002
M3 - Article
C2 - 18068350
AN - SCOPUS:37149028451
SN - 0959-8049
VL - 44
SP - 30
EP - 38
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 1
ER -