Angela DeMichele, MD, MSCE
Alan and Jill Miller Professor in Breast Cancer Excellence
Perelman School of Medicine
University of Pennsylvania
Preventing breast cancer recurrence and metastasis with targeted drug combinations to eliminate disseminated tumor cells.
Many patients treated for breast cancer later develop incurable metastatic disease, wherein their cancer has spread to other sites throughout the body. Drug resistance and subsequent metastasis are believed to be driven by a small population of cancer cells that become detached from the tumor and enter the circulation. Some enter into a process called dormancy, wherein they reach distant sites but do not grow, and are undetectable by current screening methods. How these cells exit dormancy, and generate new metastases, is unknown. The ability to therapeutically target disseminated tumor cells (DTCs) has the potential to transform outcomes for breast cancer patients. The team of Dr. DeMichele and her BCRF collaborator, Dr. Lewis, Chodosh identified a combination of targeted therapies that could eliminate DTCs. They will test them in a Phase 2 clinical trial in patients with a history of endocrine receptor (ER)–positive breast cancer.
The trial, PALAVY, which opened in summer of 2021, will treat 98 patients with one or two of three study drugs that may target dormant cells: Hydroxychloroquine to target autophagy, a survival mechanism that helps cells combat stressful conditions; Palbociclib to target the cell cycle to prevent cells from escaping dormancy; and avelumab to help the immune system attack tumor cells. The trial is enrolling patients who underwent treatment for ER-positive breast cancer, and currently have no evidence of disease, but have detectable DTCs in their bone marrow.
“This [trial] could change the current paradigm of “watchful waiting” for breast cancer survivors, providing a proactive approach to monitoring for dormant cells, and new treatments that can eradicate these cells before they can spread.”- Dr. DeMichele
Angela DeMichele, MD, MSCE, is a Professor of Medicine and Epidemiology at the University of Pennsylvania and holds the Jill and Alan Miller Endowed Professorship in Breast Cancer Excellence. Dr. DeMichele has been the Co-Leader of the Breast Cancer Research Program in the Abramson Cancer Center since 2005, where she also directs both the Breast Cancer Clinical Research Unit and the Breast Cancer TRACR Biobank. She has a dual appointment as a Senior Scholar in the Center for Clinical Epidemiology and Biostatistics, where she directs a graduate course on clinical trials and translational research and serves as thesis advisor to Masters and PhD Candidates.
As Co-Director of the 2-PREVENT Breast Cancer Translational Center of Excellence, she leads a multidisciplinary team to tackle the problem of breast cancer recurrence through novel clinical trials elucidating the role of circulating biomarkers of minimal residual disease and targeting disseminated tumor cells. She has developed numerous targeted therapies, including phase I and II development of the CDK4/6 inhibitor, Palbociclib and is currently co-PI of the international PALLAS adjuvant trial and PATINA trial for Her2+ disease. In addition, she Co-Chairs the ECOG/ACRIN Breast Committee, serves as Trial Operations Chair of the I-SPY2 multicenter, and is a member of the NCI Breast Cancer Steering Committee. She has chaired the Metastatic Breast Cancer Scientific Program and Breast Cancer and Clinical Trials Education Committees of the American Society of Clinical Oncology in addition to serving on other ASCO committees, and on the American Board of Internal Medicine Oncology Subspecialty Board. She has authored over 130 publications in high- impact journals such as NEJM and JAMA, and has been funded by the NIH, NCI, DOD, Stand Up to Cancer, Komen Foundation, Breast Cancer Research Foundation, American Society of Clinical Oncology, American Cancer Society and other philanthropic sources.
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