Editorial: Centennial Celebration – An Interview With Professor Evan Simpson on Hormones and Cancer

This month, for the Centennial Celebration of The Endocrine Society, we recognize research in the field of hormones and cancer. We have the opportunity to interview one of the leading figures in the field, Professor Evan Simpson, who is currently Director Emeritus, Hudson Institute of Medical Research, Monash Medical Centre, Melbourne, and Senior Fellow, Centre for Reproductive Health, University of Edinburgh Medical School.

Evan R.

Simpson, PhD

The topic of metabolism rose like a phoenix once more and was recognised as a driver of cancer.

Professor Simpson is a world leader in the field of estrogen biosynthesis. His work has focused on the study of aromatase, the enzyme responsible for estrogen biosynthesis. His group was the first to clone the gene encoding aromatase and to show that tissue-specific regulation was under the control of tissue-specific promoters. His research led to the concept that estrogen action in postmenopausal women is due to local production in sites such as the breast, bone, and brain. This has led to the search for drugs for breast cancer therapy that specifically inhibit aromatase expression in the breast but spare other sites where they serve a critical role, such as in the bone, brain, and blood vessels.

His current research is focused on the role of estrogen in several important health conditions, including obesity, diabetes, osteoporosis, and breast cancer.

He has been awarded honors from Endocrine Societies around the world, including the Roy O Greep Award Lecture, The Endocrine Society (United States); Asia and Oceania Medal, Society for Endocrinology (United Kingdom); Dale Medal Lecturer, Society for Endocrinology (United Kingdom); and Presidential Plenary Lecture, Endocrine Society of Australia. He has served on many committees of The Endocrine Society in both the United States and Australia and is an elected member of the Australian Academy of Science and Royal Society of Edinburgh.

Molecular Endocrinology. Let us begin the interview with your recollection of how and why you have had such a long and illustrious career in endocrinology. For many people, there is a defining moment that influences people's choice to take the path of a career academic and researcher. What was yours?

Professor Simpson. There was no defining moment for me. I always knew that this was to be the path for me. It began when I attended George Herriot's High School in Edinburgh, where my teachers of biology and chemistry ignited my passion for these subjects. When I went to the University of Edinburgh, it was a natural choice to study biochemistry, and I found the subject as exhilarating then as I do now, so endocrinology was in a sense an add-on to my passion for biochemistry.

Molecular Endocrinology. What do you consider to be seminal discoveries in the field to which you have contributed over 4 decades or more?

Professor Simpson. When I began my career the topic of hormones and cancer was all about metabolism. Then, in the 1960s, recombinant DNA technology and molecular biology emerged and as a consequence the field changed, because there were new and different tools for research discovery and investigation. These approaches dominated the field for decades, but then, almost 10 years ago, the topic of metabolism rose like a phoenix once more and was recognized as a driver of cancer. In 2011, this was formally recognized by Hanahan and Weinberg, who defined metabolism as one of the “Hallmarks of Cancer” (Hanahan D and Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674). What was fashionable at the start of my career, remerged as a highly topical and relevant subject for research endeavor in the 21st Century.

Molecular Endocrinology. What do you foresee as the next main challenge for the field?

Professor Simpson. The intersection and relationship between obesity and cancer, and inflammation and cancer.

This is because obesity is an inflammatory condition, and inflammatory mediators produced by the lipid-laden adipocytes in obese individuals drive growth of several cancers, including intestinal, endometrial, and of course breast cancer, which we have focused on. And one mechanism for this is stimulation of aromatase expression in the breast. However, such inflammatory mediators are produced in other sites also, notably the intestinal flora and the gut of obese individuals and those on a high-fat diet. Progress will involve our understanding the role of diet and the microbiome, which is very likely to show a key role for the intestinal flora in cancer.

Molecular Endocrinology. Over how many years have you contributed to The Endocrine Society? What do you think are the challenges it will face in the next 100 years?

Professor Simpson. I began my involvement with The Endocrine Society when I came to University of Texas Southwestern in Dallas as an Assistant Professor in 1977. I held various positions within the Society as my career has developed and maintained my involvement while working in the United States as well as in another country, namely Australia. There are 2 main challenges for the Society as I see it. The first is its role in the international community. How will it continue to lead, train, and educate international members when there are increasing demands and priorities set within, and by, its own United States membership? The second priority is to attract basic scientists back into the Society. With the decline in funding for basic research worldwide, young scientists have to choose very carefully which meetings they attend, and so they choose those with an emphasis on basic science. So it is critically important for the Society to make them feel that this is their “home” and that they do not feel “elbowed out” by an increasing dominance of clinicians and clinically orientated topics and presentations.