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William G. Kaelin, Jr., MD

Professor of Medicine
Dana-Farber Cancer Institute and
Brigham and Women’s Hospital,
Harvard Medical School
Boston, Massachusetts

Current Research

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 help 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 how it does that in hopes it will help him improve upon fulvestrant and also reveal ways to destroy other proteins that contribute to breast cancer.

Full Research Summary

Research area: Identifying novel treatment strategies to block estrogen-driven breast cancers.

Impact: Most breast cancer 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 aims to solve. His studies are leading to new insights into this process that may ultimately inform the development of better anti-estrogen therapies.

Current research: He and his team have been focused on characterizing the action of fulvestrant on estrogen receptor degradation and searching for other chemicals that work the same way. Their goal is to improve treatment for ER-positive breast cancers, but also to identify proteins that promote cancer growth that may also be targets for protein degradation.

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. 

What’s next: His team will characterize these new estrogen receptor degraders and complete their studies of fulvestrant. In addition, they will begin experiments aimed at determining whether two proteins that the estrogen receptor requires to function, GATA3 and FOXA1, can be degraded with drugs.

Biography

William G. Kaelin, Jr., MD 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 David Livingston’s laboratory, during which time he was a McDonnell Scholar. A Howard Hughes Medical Institute investigator since 1998, Dr. Kaelin is also currently a Professor in the Department of Medicine at the Dana-Farber Cancer Institute and the Brigham and Women’s Hospital, Harvard Medical School and Associate Director, Basic Science, for the Dana-Farber/Harvard Cancer Center.

Dr. Kaelin is a member of the National Academy of Sciences, the Institute of Medicine, the American Society of Clinical Investigation and the American College of Physicians. He recently served on the NCI Board of Scientific Advisors, the AACR Board of Trustees, and the Institute of Medicine National Cancer Policy Board. He is a recipient of the Paul Marks Prize for cancer research from Memorial Sloan Kettering Cancer Center; the Rosenthal Prize from the AACR; a Doris Duke Distinguished Clinical Scientist award; the 2010 Canada International  Gairdner Award; ASCI’s Stanley J. Korsmeyer Award; the Scientific Grand Prix the Foundation Lefoulon-Delalande; the Wiley Prize in Biomedical Sciences, and the Steven C. Beering Award; the 2016 Albert Lasker Basic Medical Research Award; the Katherine Berkan Judd Award;  and the Helis Award.

Large Researcher Headshot - Kaelin William

BCRF Investigator Since

2006

Donor Recognition

The Ulta Beauty Award

Area(s) of Focus