TY - JOUR
T1 - 50th anniversary of the first clinical trial with ICI 46,474 (tamoxifen)
T2 - Then what happened?
AU - Craig Jordan, V.
N1 - Funding Information:
This work was supported by the National 阀nstitutes of Health MD Anderson Cancer Center Support Grant (to Peter Pisters CA016672); the George and Barbara Bush Foundation for 阀nnovative Cancer Research (? C J); the Cancer Prevention Research 阀nstitute of Texas (CPR 阀T) for the STARs and STARs Plus Awards (? C J); the Dallas/Ft. Worth Living Legend Chair of Cancer Research (? C J).
Funding Information:
At the University of Leeds, I built my first tamoxifen team to address the answers to my questions supported by unrestricted funds (i.e. I was an independent university investigator not a contractor for ICI Pharmaceuticals Division). The members of my team were the final year pharmacology degree students who would conduct a one-term final year research project but then they would either become a PhD student sponsored by an ICI Pharmaceutical Division scholarship or would be employed as a technician in my laboratory. My laboratory was funded by the Yorkshire Cancer Research Campaign and ICI Pharmaceuticals Division, through my grants.
Publisher Copyright:
© 2021 BioScientifica Ltd.. All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Following the discovery and approval of the oral contraceptive, the pharmaceutical industry sought new opportunities for the regulation of reproduction. The discovery of the first non-steroidal anti-oestrogen MER25, with antifertility properties in laboratory animals, started a search for 'morning-after pills'. There were multiple options in the 1960s, however, one compound ICI 46,474 was investigated, but found to induce ovulation in subfertile women. A second option was to treat sta ge IV breast cancer. Although the patent for ICI 46,474 was awarded in the early 196 0s in the UK and around the world, a patent in the USA was denied on the basis that the claims for breast cancer treatment were not supported by evidence. A trial at the Christ ie Hospital and Holt Radium Institute in Manchester, published in 1971, showed activity compared with alternatives: High-dose oestrogen or androgen treatment, but the US Patent Office was unswayed until 1985! The future of tamoxifen to be, was in the balance in 1972 but the project went forward as an orphan drug looking for applications and a translational research strategy was needed. Today, tamoxifen is known as the first targeted therapy in cancer with successful applications to treat all stages of b reast cancer, male breast cancer, and the first medicine for the reduction of breast cance r incidence in high-risk pre- and post-menopausal women. This is the unlikely story of h ow an orphan medicine changed medical practice around the world, with millions of women's lives extended.
AB - Following the discovery and approval of the oral contraceptive, the pharmaceutical industry sought new opportunities for the regulation of reproduction. The discovery of the first non-steroidal anti-oestrogen MER25, with antifertility properties in laboratory animals, started a search for 'morning-after pills'. There were multiple options in the 1960s, however, one compound ICI 46,474 was investigated, but found to induce ovulation in subfertile women. A second option was to treat sta ge IV breast cancer. Although the patent for ICI 46,474 was awarded in the early 196 0s in the UK and around the world, a patent in the USA was denied on the basis that the claims for breast cancer treatment were not supported by evidence. A trial at the Christ ie Hospital and Holt Radium Institute in Manchester, published in 1971, showed activity compared with alternatives: High-dose oestrogen or androgen treatment, but the US Patent Office was unswayed until 1985! The future of tamoxifen to be, was in the balance in 1972 but the project went forward as an orphan drug looking for applications and a translational research strategy was needed. Today, tamoxifen is known as the first targeted therapy in cancer with successful applications to treat all stages of b reast cancer, male breast cancer, and the first medicine for the reduction of breast cance r incidence in high-risk pre- and post-menopausal women. This is the unlikely story of h ow an orphan medicine changed medical practice around the world, with millions of women's lives extended.
KW - Breast
KW - Endocrine therapy
KW - Estrogen receptor
KW - Hormone structure/function
KW - SERM
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U2 - 10.1530/ERC-20-0335
DO - 10.1530/ERC-20-0335
M3 - Review article
C2 - 33151906
AN - SCOPUS:85097962280
SN - 1351-0088
VL - 28
SP - R11-R30
JO - Endocrine-related cancer
JF - Endocrine-related cancer
IS - 1
ER -