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William G. Kaelin, Jr., MD
Sidney Farber Professor of Medicine
Dana-Farber Cancer Institute and Brigham and Women’s Hospital
Harvard Medical School
2019 Nobel Prize in Medicine
Goal: To identify new ways to treat estrogen receptor (ER)-positive breast cancer.
Impact: Dr. Kaelin is studying the anti-estrogen drug fulvestrant with an interest in understanding how it works to destroy its target, the estrogen receptor. His team is working on identifying new chemicals that have the same action in order to improve upon fulvestrant and develop new treatments for ER-positive breast cancer that has become resistant to other anti-estrogen therapies.
What’s next: He and his colleagues will test new chemicals they discovered and continue to pursue research to understand the mechanism by which fulvestrant degrades the estrogen receptor. In addition, they will begin experiments aimed at determining whether two proteins that work with the estrogen receptor can be degraded with drugs.
Patients with ER-positive breast cancers have several anti-estrogen treatment options, including fulvestrant, tamoxifen, and aromatase inhibitors. Fulvestrant works by degrading the estrogen receptor, and Dr. Kaelin is working to understand the mechanism by which it accomplishes this. His team is characterizing other chemicals that can degrade the estrogen receptor, which can potentially be used to circumvent resistance to fulvestrant and improve treatment options for patients.
Full Research Summary
Research area: Identifying novel treatment strategies to block estrogen-driven breast cancers.
Impact: Most breast cancers require estrogen to grow. Drugs such as fulvestrant, tamoxifen, and aromatase inhibitors block estrogen-driven growth and are effective treatments for ER-positive breast cancers. Fulvestrant is unique in that it also degrades the estrogen receptor on cancer cells. How it does this has been a longstanding mystery that Dr. Kaelin is focused on solving. His studies are leading to new insights into this process that may ultimately inform the development of better anti-estrogen therapies.
Current investigation: Dr. Kaelin and his team are determining the mechanism of fulvestrant degradation of the estrogen receptor and searching for other chemicals that work the same way. In addition, they have identified two proteins which are required for estrogen receptor function and will determine if degradation of these proteins is possible with existing drugs.
What he’s accomplished so far: Dr. Kaelin has successfully identified chemicals with the same action as fulvestrant and made new discoveries relating to the mechanism by which fulvestrant destroys the estrogen receptor. He has also identified two other proteins, GATA3 and FOXA1, that are required by the ER and therefore potential targets for new drug development.
What’s next: His team will characterize these new estrogen receptor degraders and complete their studies of fulvestrant. In addition, they will continue their studies to determine whether two proteins that the estrogen receptor requires to function, GATA3 and FOXA1, can be degraded with drugs.
William Kaelin, Jr., MD is the Sidney Farber Professor of Medicine in the Department of Medicine at the Dana-Farber Cancer Institute and the Brigham and Women’s Hospital, Harvard Medical School and a Howard Hughes Medical Institute investigator since 1998. He obtained his undergraduate and MD degrees from Duke University and completed training in internal medicine at the Johns Hopkins Hospital, where he served as chief medical resident. He was a clinical fellow in medical oncology at the Dana-Farber Cancer Institute and later a postdoctoral fellow in David Livingston’s laboratory, during which time he was a McDonnell Scholar.
Among his many distinguished awards, Dr. Kaelin is the 2019 Nobel Prize recipient in Physiology or Medicine for his discoveries of how cells sense and adapt to oxygen availability. These findings have paved the way for promising new strategies to fight a wide range of disorders, including cancer, cardiovascular disease, anemia and many others.
Other notable honors include the 2018 Massry Prize given by the Meira and Shaul G. Massry Foundation to recognize his outstanding contributions to the biomedical sciences and the advancement of health; the 2016 Lasker Award for medical science; the Grand Prix of the Fondation Lefoulon-Delalande from the Institute of France in 2012 and the 2010 Canada Gairdner International Award for his contributions to the field of cardiovascular research. He also received the Helis Award in 2018, and the Science of Oncology Award from the American Society of Clinical Oncology and the Princess Takamatsu Award from the American Association for Cancer Research, both in 2016.
Dr. Kaelin is a member of the National Academy of Sciences, the National Academy of Medicine, the American Society of Clinical Investigation and the American College of Physicians and a Fellow of the AACR Academy. He recently served on the NCI Board of Scientific Advisors, the AACR Board of Trustees, and the Institute of Medicine National Cancer Policy Board.
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