Titles and Affiliations
Director, Massachusetts General Hospital Cancer Center
Kurt J. Isselbacher Professor of Oncology, Harvard Medical School
Investigator, Howard Hughes Medical Institute
Research area
Using circulating tumor cells captured from a simple blood draw to understand and monitor drug resistance in advanced breast cancer.
Impact
The most common type of breast cancer, hormone receptor (HR)-positive breast cancer, is initially highly responsive to treatment. However, tumor cells can eventually become resistant to multiple courses of hormone therapy, and all too often, the cancer spreads and becomes unresponsive to all therapeutic options. To study advanced, drug-resistant HR-positive breast cancer, Dr. Haber and his team use circulating tumor cells (CTCs), which are cancer cells caught in the bloodstream. The team has engineered highly sophisticated microfluidic devices that successfully capture CTCs. The tumor cells remain viable, and the team has been able to grow them in the laboratory and interrogate them at different stages of patient treatment. This approach offers a unique, non-invasive way to understand how breast cancer becomes resistant to therapy and to identify vulnerabilities that could be targeted with new or existing drugs.
Progress Thus Far
The team is focused on two complementary strategies. First, they analyzed CTCs from the blood of patients with advanced breast cancer receiving antibody-drug conjugates (ADCs), a treatment approach that links an antibody to a chemotherapy drug allowing it to bind selectively to cancer cells and deliver chemotherapy directly to the tumor. The team found that CTC testing was informative for some ADCs, where target protein levels closely tracked with treatment outcomes, but not for others, where the protein levels didn’t correlate with outcomes at all. This suggests CTC testing may prove useful as a predictive tool for select ADCs, rather than universally.
Second, the team continued to study how advanced breast cancers lose their reliance on the estrogen receptor pathway and become resistant to hormone therapies. CTCs grown in the laboratory recreate the biological features of advanced, heavily treated breast cancer, offering a valuable tool for identifying new treatments for patients whose cancer no longer responds to standard therapies.
What’s Next
The team’s goals for the coming year are to expand their CTC-based test to evaluate new treatment targets as additional ADCs become available. They will use their lab-created CTCs to understand why cancer cells stop producing the estrogen receptor as they become treatment-resistant, and whether this process can be reversed. Success in either of these areas could significantly impact treatment strategies for patients with advanced breast cancer.
Biography
Daniel A. Haber, MD, PhD is Director of the Massachusetts General Hospital (MGH) Cancer Center and the Kurt J. Isselbacher Professor of Oncology at Harvard Medical School. His research interests have focused on applying cancer genetics toward clinically relevant challenges. Dr. Haber received his PhD and MD degrees at Stanford in 1981 and 1983, respectively. He completed an internal medicine residency at MGH, clinical oncology training at the Dana-Farber Cancer Institute, and postdoctoral research at MIT. He joined the faculty of Harvard Medical School and MGH Cancer Center in 1991. Dr. Haber’s numerous awards include a MERIT Award from the National Cancer Institute, the Doris Duke Distinguished Clinical Scientist Award, and a Dream Team Award from Stand Up To Cancer. He was appointed to the Howard Hughes Medical Institute in 2008 and elected to the Institute of Medicine/National Academy of Medicine in 2009, the American Academy of Arts and Sciences in 2011, the National Academy of Sciences in 2018, and as a Fellow of the American Association of Cancer Research in 2019.
