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Breast cancer scientist receives award for translational research
V. Craig Jordan, OBE, DSc, PhD, the Dallas/Ft. Worth Living Legend Chair of Cancer Research and professor of breast oncology and molecular and cellular oncology at The University of Texas MD Anderson Cancer Center, was awarded the Gerald D. Aurbach Award for Outstanding Translational Research by the Endocrine Society at its annual meeting.
The award recognizes outstanding contributions to research that propel the translation of scientific discoveries into clinical applications.
Jordan, considered the “father of tamoxifen,” a groundbreaking drug in the treatment of breast cancer, was celebrated for the discovery and development of selective estrogen receptor modulators (SERMs). These drugs, which provide the benefits of estrogen while bypassing the hormone’s potential adverse effects, are administered in the treatment and prevention of major diseases in women.
Endocrine Today spoke with Jordan about both the challenges and the triumphs he has experienced throughout his career.
What was the defining moment that led you to your field?
Jordan: In 1969, I had completed my bachelor’s degree in the pharmacology department at Leeds University in England. I had been awarded a medical research council scholarship to complete a simple and straightforward study. My supervisor, Edward R. Clark, PhD, had read the seminal publications by Jack Gorski, PhD, in the Proceedings in the National Academy of Sciences about the isolation of the rat uterine estrogen receptor as a soluble protein. He had obtained a substantial equipment grant for me to isolate the estrogen receptor and crystalize it with estradiol or an anti-estrogen that at that time were failed contraceptives. Anti-estrogens were perfect morning-after pills in animals, but did the opposite in women by inducing ovulation. I was to do the X-ray crystallography at the Astbury Department of Biophysics and solve the simple problem of how the complex changes when an antagonist binds to the estrogen receptor. Well, that did not work. Only part of the estrogen receptor was resolved in the late 1990s. I received a PhD in estrogen action and failed contraceptives! This training and background, however, prepared me for the future. I went off to the Worcester Foundation for Experimental Biology (WFEB) to learn more about contraception. However, what I wanted to do was to develop drugs to treat cancer.
What has been the greatest challenge in your professional career thus far?
Jordan: In 1972, I was recruited to be a tenure track lecturer at Leeds University, but first I was required go to the WFEB for 2 years to learn new science and techniques. However, there was a problem. My department could find no one in the United Kingdom willing to examine my PhD on “failed contraceptives,” and without a PhD my future was nonexistent.
Finally, it was agreed that Arthur L. Walpole, PhD, former head of the reproduction and fertility control program at ICI Pharmaceuticals Division, would be appropriate, as he had just published on a new compound — ICI46,474. With reluctance, he was approved by Leeds University. Armed with my PhD, I arrived at the WFEB to find I had no supervisor and was told to plan 2 years of work before returning to Leeds. A phone call to Walpole about turning ICI46,474 into a breast cancer drug was met with his support. I was tasked for the next 7 years of support by ICI with developing a strategy to use its orphan drug in the clinic. I was fortunate to meet and be mentored by both William L. McGuire, MD, and Elwood V. Jensen, PhD, who taught me all the necessary techniques to complete my strategic plan.
What are some of the most exciting advances that you have been a part of?
Jordan: The strategy I proposed for the clinical development for tamoxifen was to treat only estrogen receptor-positive breast cancers using long-term adjuvant tamoxifen therapy (forever). I raised the possibility that tamoxifen could prevent breast cancer as described in my publications in the 1970s.
I presented my treatment strategy at a medical conference in Cambridge, and I was considered dangerous with this new idea based on animal studies. By contrast, the following month, I presented the same lecture at the University of Wisconsin, Madison, at its cancer center. The leadership team of Paul P. Carbone, MD, and Harold Rusch, MD, immediately offered me a job. I became director of its breast cancer program.
My strategy today is FDA approved and standard of care. At Wisconsin, all of the planets lined up with our laboratory work, and we discovered the pharmacology of SERMs. SERMs are estrogens or anti-estrogens in different tissues around a woman’s body. We discovered that a failed breast cancer drug could prevent osteoporosis and prevent breast cancer at the same time. Raloxifene was born. There are five FDA-approved SERMs that all have chemical connections to my work at Wisconsin.
What advice would you offer to a student going into the field today?
Jordan: The advice I give is based on a lecture I present, titled “Scientific Survival Suggestions.” First, carefully decide on your mentor or supervisor for your doctorate. Second, train yourself to ascend in science. Third, get documentation that says what you can do. Fourth, recognize that experiments are a conversation with nature. Fifth, follow your instincts about what you want to achieve; have a goal. Sixth, know an opportunity when you are presented with unsettling change. Seventh, give chances to allow your team members to excel, encourage them to do work that merits publication. Eight, understand that it is your responsibility to obtain support for your science and your team. Ninth, although science can be distracting, publish or perish. Tenth, when you publish, your colleagues and competitors will often ignore your landmark work.
In the case of No. 3, I learned at an early age from my schoolmasters that everything you do to excel must be documented. In No. 4, if all of your controls are reproducible, but the experiment does not give you the answer you anticipated, then this is a discovery. This has happened several times in my own laboratory.
What are your hobbies/interests outside of work?
Jordan: If I were not a medical scientist, I would have drifted toward being a historian and had plans to be an archeologist. Additionally, because of my family background, I grew up in an environment of military service to the nation. I served as a regular army reserve officer in special forces until the age of 55 years, so that was all-consuming whilst competing for an academic career and leading research teams. I get great enjoyment out of my library of 6,000 hardback history and science books and correspondence with authors that include soldiers, scientists, television presenters in archeology and science, and one spy. Five or 6 years ago, before I came to Texas, I would frequently spend months in the mountains in Austria and southern Germany; I hope to get back to that.
Disclosure: Jordan reports no relevant financial disclosures.