Fred Hutchinson Cancer Research Center
Executive Vice President for Clinical Affairs
Senior Vice President and Director, Clinical Research Division
Professor and Head, Department of Medicine, Division of Medical Oncology
BCRF Scientific Advisory Board, Member Emeritus
Seeking to understand and overcome drug resistance in aggressive breast cancers that frequently affect younger women and women of color.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionately affects young Black and Hispanic women. It is also the most common breast cancer in women with inherited mutations in the BRCA genes, who also tend to be diagnosed early in life. While few targeted therapies currently exist for TNBC and BRCA-driven breast cancers, some TNBC can be treated with chemotherapy, and PARP inhibitors are effective at targeting the key cancer-causing defect in BRCA-mutant breast cancers. Despite this, however, many tumors will not respond to these therapies (called intrinsic resistance) or become resistant during the treatment (called acquired resistance). To address this urgent need, Dr. Davidson’s team is seeking ways to understand the causes of resistance and to devise strategies to make these therapies more effective. In the case of chemo-resistance, her team is characterizing the tumor immune microenvironment (TIME) of TNBC tumors to find ways to convert an immunologically “cold” (lacking immune response) TIME to a “hot” one that will make the tumor responsive to chemotherapy. In the case of PARP inhibitor resistance, Dr. Davidson’s team is seeking to identify biomarkers that can be used to identify which patients are most likely to benefit from PARP inhibitor therapy. Collectively, these studies may lead to better management of these aggressive breast cancers.
Dr. Davidson’s team has examined the myeloid cell subpopulation (including macrophages and neutrophils) in the TIME and discovered that they are present in abundance in chemotherapy resistant TNBC. To do this, they utilized a unique resource of TNBC samples from patients before and after neo-adjuvant therapy and compared the TIME pre- and post-treatment to identify intrinsic versus acquired mechanisms of resistance. They then correlated the types of immune cells present with resistance and clinical outcomes. Analyses are ongoing to validate these findings, but the results will potentially inform effective combination strategies for treating this aggressive subtype. In related work Dr. Davidson is leveraging positron emission tomography (PET), a non-invasive imaging technology, to predict PARP inhibitor benefit. In metastatic disease, there are genetic variations in tumor cells that emerge over time within an individual. Using a molecular imaging biomarker, one that binds to the PARP protein, the team can follow changes in PARP protein in the primary tumor compared to its metastases. She and her colleagues have developed a clinical trial protocol for this study and are currently acquiring necessary institutional approvals.
Ongoing studies on the TIME will likely reveal how its composition relates to patient prognosis and therapy response. In the next year, Dr. Davidson and her colleagues will open the PET scan clinical trial to examine strategies for selecting patients for PARP inhibitor treatment beyond BRCA mutation status. In the aggregate, their studies will provide insights on ways to improve the effectiveness of targeted therapies such as PARP inhibitors, giving the “right treatment” to the “right patient” at the “right time” and significantly impacting cancer control and patient survival.
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.
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