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Angela DeMichele, MD, MSCE
Professor of Medicine and Epidemiology
Perelman School of Medicine
University of Pennsylvania
Seeking to prevent breast cancer recurrence and metastasis with targeted drug combinations to eliminate disseminated tumor cells (DTC).
A clinical trial is planned to identify biologic features that will predict response to treatment.
The ability to identify, characterize and therapeutically target DTCs has the potential to transform outcomes for breast cancer patients.
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. Disseminated tumor cells (DTCs) detected in the bone marrow of patients after treatment is a sign of poor outcome. Drs. DeMichele and Chodosh have identified a combination of targeted therapies that destroys DTCs in laboratory models. Their current research moves this discovery to a Phase I clinical trial to test this strategy in patients with advanced breast cancer.
Full Research Summary
Many patients treated for breast cancer later develop incurable metastatic disease. The goal of Dr. DeMichele’s BCRF research is to prevent breast cancer recurrence by detecting and targeting a subset of cells called disseminated tumor cells (DTCs) that can survive treatment, hibernate in the bone marrow and form new tumors years later.
Studies have shown that these cells can survive through “autophagy,” a process in which cells survive on internal energy sources. mTOR, a signaling protein that sends signals from the cell surface to the nucleus further enables the cells to maintain the machinery required for growth.
Dr. DeMichele and BCRF collaborator Lewis Chodosh will determine whether drugs targeting autophagy and/or mTOR in women harboring DTCs after neoadjuvant (pre-surgery) treatment will reduce or eliminate these cells.
The ability to identify, characterize and therapeutically target DTCs in breast cancer patients has the potential to prevent tumor recurrence, metastasis and mortality, transforming surveillance and treatment.
Dr. DeMichele 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. Her research program is focused on drug development, innovative clinical trial design and investigation of biomarkers for precision therapy. 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 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 serves as Trial Operations Chair of the I-SPY2 multicenter, neoadjuvant trial, Penn site PI for the Translational Breast Cancer Research Consortium and on the Breast Core Committee of ECOG/ACRIN. She has authored over 130 publications in impact journals such as NEJM and JAMA, and has been funded by the NIH, NCI, DOD, Komen Foundation, Breast Cancer Research Foundation, American Society of Clinical Oncology, American Cancer Society and other philanthropic sources. 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 is an Associate Editor at Breast Cancer Research.