TY - JOUR
T1 - Turning scientific serendipity into discoveries in breast cancer research and treatment
T2 - a tale of PhD students and a 50-year roaming tamoxifen team
AU - Jordan, V. Craig
N1 - Funding Information:
On September 20th, the American Association for the Advancement of Science announced the selection of V. Craig Jordan to be the 2021 recipient of the Golden Goose award. This award recognizes research completed with federally funded research grants that resulted in scientific discoveries that improved patient care, patient survival enhanced the development of medicines and improved economic growth for the Nation. This retrospective recounts that journey. I express my gratitude to Sir Alan Wilson, the then Vice Chancellor of the University of Leeds, and the late Dr. Barry JA Furr, Chief Scientist of AstraZeneca, for their nominations of my contributions to advancing tamoxifen through translational research that resulted in the award of Officer of the Most Excellent Order of the British Empire (OBE 2002) for services to international breast cancer research and Sir Alan Langlands, Vice Chancellor of the University of Leeds, for his nomination for my appointment as Companion of the Most Distinguished Order of St. Michael and St. George (CMG 2019) for services to women’s health.
Funding Information:
The studies described in this retrospective were funded by both peer-reviewed grant funding from the NCI/NIH/DoD or the generosity of the Lynn Sage Foundation for Breast Cancer Research, the AVON Foundation, and the Susan G. Komen Breast Cancer Foundation. The investment of both taxpayers money and major philanthropic organizations in the discovery and maturation of unlikely research projects on breast cancer resulted in not only millions of women’s lives extended or saved worldwide but also mechanistic insights into the new science of SERMs and cutting the Gordian knot of the WHI. Women’s health was improved worldwide because of government’s investment in projects without an obvious initial benefit to mankind. Benefit came through the pharmaceutical industry eventually realizing the potential of the new science. Five FDA-approved medicines (SERMs) resulted, jobs were created, and economic wealth realized. The formula has worked dramatically to benefit women and the families for which they care. This story is a prime example for the value of “investing in the young and talented” to enrich the Nation and the World. This work was supported by NIH Grants CA-32713 (VCJ), CA-56143 (VCJ), CA-14520 (PPC), PO1-CA20432, 5T32-CA09471 (VCJ), BC050277 Center of Excellence (VCJ), Specialized Program of Research Excellence (SPORE) grant CA-89018 in breast cancer (VCJ), Department of Defense Training grant in breast neoplasia DA MD17-00–5671-0386 (VCJ), Signal Transduction Training grant T32-CA70085-06 (VCJ), Department of Defense Breast Program BC 050277 Center of Excellence (VCJ), the SU2C/AACR grant (VCJ), Susan G. Komen Scholar’s Award (VCJ), the Lynn Sage Breast Cancer Foundation of the RH Lurie Comprehensive Cancer Center (VCJ), the Avon Foundation (MM, VCJ), the National Institute of Health, National Cancer Institute, MD Anderson Cancer Center Support Grand (CA 016672), to Peter Pisters, MD; the George and Barbara Bush Foundation for Innovative Cancer Research (VCJ), the Cancer Prevention Research Institute (CPRIT) for the Science and Technology Acquisition and Retention (STARs) and STARs Plus Award (VCJ); the Diana, Princess of Wales Professor of Cancer Research, the Alfred G Knudson Chair in Basic Science, VT Lombardi Chair of Cancer Research, and the Dallas/Fort Worth Living Legend Chair of Cancer Research (VCJ). I thank my Senior Administrative Assistant Victoria VanGordon for her diligence during the preparation of this manuscript and Dr. Philipp Maximov for his indispensable assistance in preparation of the figures and the new edited manuscript.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/11
Y1 - 2021/11
N2 - Purpose: This retrospective, about a single “mobile” laboratory in six locations on two continents, is intended as a case study in discovery for trainees and junior faculty in the medical sciences. Your knowledge of your topic is necessary to expect the unexpected. Historical method: In 1972, there was no tamoxifen, only ICI 46, 474, a non-steroidal anti-estrogen with little chance of clinical development. No one would ever be foolish enough to predict that the medicine, 20 years later, would achieve legendary status as the first targeted treatment for breast cancer, and millions of women would benefit from long-term adjuvant tamoxifen therapy. The secret of tamoxifen’s success was a translational research strategy proposed in the mid 1970’s. This strategy was to treat only patients with estrogen receptor (ER)-positive breast cancer and deploy 5 or more years of adjuvant tamoxifen therapy to prevent recurrence. Additionally, tamoxifen prevented mammary cancer in animals. Could the medicine prevent breast cancer in women? Results: Tamoxifen and the failed breast cancer drug raloxifene became the first selective estrogen receptor modulators (SERMs): a new drug group, discovered at the University of Wisconsin, Comprehensive Cancer Center. Serendipity can play a fundamental role in discovery, but there must be a rigorous preparation for the investigator to appreciate the possibility of a pending discovery. This article follows the unanticipated discoveries when PhD students “get the wrong answer.” The secret of success of my six Tamoxifen Teams was their technical excellence to create models, to decipher mechanisms, that drove the development of new medicines. Summary of advances: Discoveries are listed that either changed women’s health or allowed an understanding of originally opaque mechanisms of action of potential therapies. These advances in women’s health were supported entirely by government-sponsored peer-reviewed funding and major philanthropy from the Lynn Sage Breast Cancer Foundation, the Avon Foundation, and the Susan G. Komen Breast Cancer Foundation. The resulting lives saved or extended, families aided in a time of crisis and the injection of billions of dollars into national economies by drug development, is proof of the value of Federal or philanthropic investment into unencumbered research aimed at saving millions of lives.
AB - Purpose: This retrospective, about a single “mobile” laboratory in six locations on two continents, is intended as a case study in discovery for trainees and junior faculty in the medical sciences. Your knowledge of your topic is necessary to expect the unexpected. Historical method: In 1972, there was no tamoxifen, only ICI 46, 474, a non-steroidal anti-estrogen with little chance of clinical development. No one would ever be foolish enough to predict that the medicine, 20 years later, would achieve legendary status as the first targeted treatment for breast cancer, and millions of women would benefit from long-term adjuvant tamoxifen therapy. The secret of tamoxifen’s success was a translational research strategy proposed in the mid 1970’s. This strategy was to treat only patients with estrogen receptor (ER)-positive breast cancer and deploy 5 or more years of adjuvant tamoxifen therapy to prevent recurrence. Additionally, tamoxifen prevented mammary cancer in animals. Could the medicine prevent breast cancer in women? Results: Tamoxifen and the failed breast cancer drug raloxifene became the first selective estrogen receptor modulators (SERMs): a new drug group, discovered at the University of Wisconsin, Comprehensive Cancer Center. Serendipity can play a fundamental role in discovery, but there must be a rigorous preparation for the investigator to appreciate the possibility of a pending discovery. This article follows the unanticipated discoveries when PhD students “get the wrong answer.” The secret of success of my six Tamoxifen Teams was their technical excellence to create models, to decipher mechanisms, that drove the development of new medicines. Summary of advances: Discoveries are listed that either changed women’s health or allowed an understanding of originally opaque mechanisms of action of potential therapies. These advances in women’s health were supported entirely by government-sponsored peer-reviewed funding and major philanthropy from the Lynn Sage Breast Cancer Foundation, the Avon Foundation, and the Susan G. Komen Breast Cancer Foundation. The resulting lives saved or extended, families aided in a time of crisis and the injection of billions of dollars into national economies by drug development, is proof of the value of Federal or philanthropic investment into unencumbered research aimed at saving millions of lives.
KW - Estrogen receptor
KW - Raloxifene
KW - Selective estrogen receptor modulators
KW - Tamoxifen
KW - Women’s Health Initiative
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U2 - 10.1007/s10549-021-06356-8
DO - 10.1007/s10549-021-06356-8
M3 - Review article
C2 - 34398352
AN - SCOPUS:85112570554
SN - 0167-6806
VL - 190
SP - 19
EP - 38
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -