Mitch Dowsett, PhD, BSc
Professor of Biochemical Endocrinology; Head of the Academic Department of Biochemistry and Head of Breast Cancer Translational Research
Royal Marsden Hospital and Institute of Cancer Research, London, England
2008-2009 BCRF Project:
(made possible by generous support from Delta Air Lines, Inc.)
Co-Investigator:
Ian E. Smith, MD, FRCP, Royal Marsden Hospital and Institute of Cancer Research, London, England
Over the last few years a group of hormone-blocking agents, the aromatase inhibitors (AIs: Anastrozole, Letrozole and Exemestane), have increasingly replaced Tamoxifen as first line hormone treatment of choice for postmenopausal women with early breast cancer. The overall aim of the work of Drs. Smith and Dowsett is to enable clinicians to identify more accurately which patients are most likely to benefit from, or conversely to be resistant to, AIs and to better understand the biology that underpins this behaviour.
They previously assessed the expression of about 20,000 genes in a series of patients treated with an AI in the advanced breast cancer setting and results were obtained on 58 tumours. This identified 183 genes and 11 biological pathways that were expressed differently between responders and non-responders. Of particular interest the androgen-estrogen metabolism pathway was the most different and this difference was explained largely by the different expression of a gene (HSD17B7) that converts the low-activity estrogen, estrone, to the high-activity estrogen, estradiol.
The scientists are now determining whether this observation can be confirmed in a larger series of fixed samples prior to assessing whether this may form a viable target for treatment with or without AI. In parallel with this they have finalised the construction of tissue microarrays (TMAs) from a total of nearly 400 samples of fixed tissue from AI-treated patients and have used these to characterise the response to AIs according to their expression of estrogen receptor (ER), progesterone receptor (PgR) and HER2. In addition they are investigating these same pathways and genes in patients who have been treated with an AI prior to surgery.
Bio:
Professor Mitchell Dowsett is Professor of Biochemical Endocrinology, Head of the Academic Department of Biochemistry and Head of Breast Cancer Translational Research at the Royal Marsden Hospital and the Institute of Cancer Research.
His research interests are predominantly in endocrine aspects of breast cancer and in biomarker evaluation and application. He has a laboratory research team of approximately 25, all of whom are focused on translational aspects of breast cancer research.
Professor Dowsett is the founding chairman of the UK National Cancer Research Institute Translational Clinical Study Group, which aims to enhance Translational Research across the countries clinical trial portfolio in cancer. He is a member of the Steering and Executive Committees of several prominent international breast cancer trials including ATAC and HERA for which he is chairman of the translational research committees. Membership of a number of peer-review committees includes the Scientific Committees of Cancer Research Ireland and the Danish Cancer Society.
He is the author of over 430 professional papers.
