Titles and Affiliations
Executive Vice President for Clinical Affairs and Professor
Professor, Department of Medicine
Raisbeck Endowed Chair for Collaborative Cancer Research
University of Washington
Research area
Improving immunotherapies for breast cancer.
Impact
The success of immunotherapy to treat breast cancer has been hampered by the ability of tumor cells to adapt and evade a person’s immune system. Researchers, including Dr. Nancy Davidson, are seeking ways to improve its use in breast cancer by specifically targeting a process used by tumors to help them survive an immune response. It has been shown that the protein nuclear factor erythroid-related factor 2 (NRF2) can help protect normal cells from damage. However, NRF2 can also protect cancer cells, allowing them to hide from the immune system and making immunotherapy less effective. In fact, Dr. Davidson and her colleagues have found that NRF2 is more active in breast cancer cells and is linked to worse outcomes for patients. Her team will explore ways to target NRF2 and make breast cancers more visible and vulnerable to the immune system. Dr. Davidson’s findings could lead to more effective treatments for patients with breast cancer, especially those who have not benefited from traditional therapies. She not only strives to advance therapeutic options for breast cancer but also aims to uncover fundamental insights into the complex interplay between cancer biology and immune responses.
Progress Thus Far
Dr. Davidson’s team has devised a groundbreaking strategy to block NRF2 in laboratory models of breast cancer and evaluate its impact, particularly in combination with immune therapies. In the past year, her team created new breast cancer cell lines in which NRF2 can be rapidly turned off using a specialized drug system. These models allow precise control of NRF2 levels in tumor cells. In breast tumors with high NRF2 levels, they found that turning off NRF2 slows tumor growth and alters the types of immune cells that are present in the tumor microenvironment. Specifically, fewer neutrophils—a type of inflammatory cell—and more CD4 “helper” T cells—crucial for the activity of other immune cells—were observed in tumors lacking NRF2. Removing these CD4 cells restored tumor growth, showing they play a key role in the immune response triggered by NRF2 loss. Finally, they tested whether tumors with high NRF2 levels resist immune checkpoint inhibitor (ICI) therapy, a key form of immunotherapy. These tumors responded poorly to treatment, supporting the idea that NRF2 contributes to an immune-suppressive environment in breast cancer.
What’s Next
Dr. Davidson and her colleagues will continue to explore how the NRF2 pathway influences whether breast tumors respond to or resist treatment with ICIs, a powerful class of cancer immunotherapy. Prior work focused on NRF2 activity within tumor cells, and they will now investigate whether NRF2 also affects immune cells in the tumor microenvironment that help control cancer. To accomplish this, they engineered novel laboratory models where the NRF2 pathway in specific immune cells can be selectively turned off or on. These models provide a unique vehicle for determining how NRF2 affects the function of key immune cell types that are known to be important for driving anti-tumor immune responses. Further, they may help to determine whether NRF2 plays a helpful or harmful role in immune cells’ ability to attack cancer, which is particularly important since NRF2-blocking drugs are being developed for cancer therapy. These results will provide critical insight into how such drugs might affect not just tumor cells, but also the immune system’s natural ability to fight cancer. Further, they may help explain how NRF2 shields tumors from the immune system and point to new strategies for improving breast cancer treatment.
Biography
Dr. Davidson is a world-renowned breast cancer researcher who serves as Senior Vice President and Director of the Clinical Research Division at the Fred Hutchinson Cancer Research Center, President and Executive Director of the Seattle Cancer Care Alliance, and Head of the Division of Medical Oncology at the University of Washington.
Dr. Davidson has published key findings on the role of hormones, particularly estrogen, on gene expression and cell growth in breast cancer. She has guided several important national clinical trials of new therapies for breast cancer, including chemo-endocrine therapy for premenopausal breast cancer. Her research has been supported by a portfolio of funding from the National Institutes of Health (NIH), Department of Defense, the Breast Cancer Research Foundation, and Susan G. Komen for the Cure. She has authored over 350 articles in the top journals of her field.
An elected member of the Association of American Physicians, National Academy of Medicine, and the American Academy of Arts and Sciences, Dr. Davidson is an active member of the scientific advisory boards as well as external advisory boards of many foundations and cancer centers. She has also served as an elected member of the Board of Directors of the American Association of Cancer Research (AACR) and the American Society of Clinical Oncology (ASCO) – the two largest organizations for cancer researchers and oncology professionals in the world. She was President of ASCO from 2007 to 2008 and President of AACR from 2016 to 2017.
Dr. Davidson earned her MD degree from Harvard Medical School and completed her internal medicine internship at the Hospital of the University of Pennsylvania and internal medicine residency at Johns Hopkins Hospital. Subsequently, Dr. Davidson completed a medical oncology fellowship at the NIH’s National Cancer Institute. She was a faculty member in the Department of Oncology at the Johns Hopkins University School of Medicine from 1986 to 2009, serving as Director of the Breast Cancer Program from 1994 to 2009 and as the Breast Cancer Research Chair of Oncology at Johns Hopkins University School of Medicine from 1995 – 2009. From 2009-2016 she served as Hillman Professor of Medicine and Associate Vice Chancellor for Cancer Research at the University of Pittsburgh and Director of the University of Pittsburgh Cancer Institute.
