The Royal Marsden Hospital and Institute of Cancer Research London, United Kingdom
Head, Department of Biochemistry and Centre for Molecular Pathology Professor of Biochemical Endocrinology, Breakthrough Research Centre Professor of Translational Research Emeritus
Developing new strategies to prevent resistance to estrogen-targeted therapies.
The majority of breast cancers depend on estrogen for growth and are called estrogen receptor (ER)-positive. Inhibiting the production of estrogens or blocking their effect with anti-estrogen agents (such as an aromatase inhibitor or tamoxifen) markedly reduces growth of ER-positive breast cancers—these agents can reduce the chance of death by 30 to 40 percent. It is critical to determine which patients have a good chance of benefiting from these therapies and those that do not. Drs. Dowsett and Smith are conducting studies to define the immune features of those tumors that become resistant to endocrine therapy. This will help to inform treatment decisions and improve outcomes for patients.
Drs. Dowsett and Smith have found that multiple signals from immune components of the tumor microenvironment are essential for continued tumor growth. They are characterizing those immune features and will seek to specifically identify those associated with resistance to aromatase inhibitors. They will also determine which new immunotherapy drugs could be used to reverse that resistance and enhance outcomes for patients with ER-positive breast cancer or those that should be avoided because they enhance drug resistance.
“Without BCRF support we would not have had the freedom to pursue unusual or risky concepts that have, over nearly 20 years, resulted directly and indirectly to our conduct of major clinical studies, leveraging of other funds, and several seminal findings for the benefit of breast cancer patients.” — Dr. Dowsett
Professor Mitch Dowsett, FMedSci, PhD, is Head of the Academic Department of Biochemistry and Head of the Centre for Molecular Pathology at the Royal Marsden Hospital; Professor of Biochemical Endocrinology at the Institute of Cancer Research; and Professor of Translational Research in the Breakthrough Breast Cancer Centre, London.
Professor Dowsett’s research focuses almost exclusively on breast cancer and predominantly on hormonal aspects of the disease and biomarkers of response with a research team of about 24 investigators. He was closely involved with the clinical development of aromatase inhibitors and in the creation of national and international standards for steroid receptor and HER2 analysis (ASCO/CAP Guidelines Steering Committees). He co-chairs the International Working Party for Ki67 in Breast Cancer. He was the founding chairman of the UK NCRI Translational Research (subsequently Biomarker and Imaging) Clinical Study Group. In 2004 he founded and continues to chair the Aromatase Inhibitor Overview Group.
He has authored nearly 600 published papers related to breast cancer, and given numerous named lectures including the 2007 William L McGuire Memorial Lecture. He served on the Executive Board of the Breast International Group (BIG) for seven years, and currently sits on the Executive/Steering Committees of several clinical trials. He has been a NCRI Senior Clinical Investigator since 2009. In 2013, he was appointed as a Fellow of the Academy of Medical Sciences.
2006
The Royal Marsden Hospital London, United Kingdom
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