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Clodia Osipo, PhD
Associate Professor, Department of Pathology
Member, Breast Cancer Basic Science Program
Member, Cancer Immunology Research Program
- Targeting breast cancer stem cells to prevent resistance to treatments for estrogen receptor-positive breast cancers.
- Studies are ongoing to identify the drivers of endocrine resistance for future clinical trials.
- Strategies to block survival of dormant cancer stem cells will improve patient outcomes.
Endocrine (anti-hormone) therapies are effective treatment for breast cancers that rely on estrogen for growth, but resistance to these therapies often develops. Breast cancer stem cells are specialized cells that make up a small fraction of cells in a tumor but are responsible for drug resistance and recurrences. Drs. Albain and Osipo have identified a potential strategy to block cancer stem cells through a targeted approach.
Full Research Summary
Breast cancer consists of several subtypes defined by tumor biomarkers: hormone receptor-positive (ER/PR), HER2-positive, or triple negative (lacking ER, PR, and HER2). ER-positive subtypes are treated with endocrine therapy, such as tamoxifen or aromatase inhibitors. However, resistance to endocrine therapy remains a major clinical concern as drug-resistant tumors continue to grow and are more likely to spread to other organs (metastasize).
Drs. Albain and Osipo have been studying the role of the Notch signaling pathway in breast cancer for more than a decade and have shown that Notch is responsible for resistance to endocrine and anti-HER2 therapy. This could be due to its role in helping breast cancer stem cells survive. These stem cells lay dormant and evade therapy, ultimately causing tumor progression upon reactivation.
They recently discovered a novel treatment that targets Notch and causes a decrease in breast cancer stem cells. They have also identified a potential biomarker called DAXX that may predict response to this treatment in patients.
Their ongoing studies suggest that endocrine therapy, while effective at shrinking tumors, may also promote survival of breast cancer stem cells through an interaction between Notch and DAXX. This year, the team will investigate which of these genes drives breast cancer stem cells during endocrine therapy. With this information the team will be able to design treatments to prevent resistance to endocrine therapy. Furthermore, Notch and DAXX together could also serve as biomarkers to select patients for a future clinical trial of a combination therapy with a Notch inhibitor plus other targeted therapies.
Overall, strategies to block survival of dormant cancer stem cells will improve patient outcomes
Dr. Clodia Osipo received her PhD in Molecular and Cellular Biochemistry from Loyola University in 2002 while working under Dr. Allen Frankfater. Thereafter, she did her post-doctoral fellowship at the Robert H. Lurie Comprehensive Cancer Center of the Feinberg School of Medicine at Northwestern University. Dr. V. Craig Jordan, the principal developer of adjuvant tamoxifen therapy for estrogen receptor positive breast cancer, was her mentor. Dr. Osipo's research under Dr. Jordan focused on investigating the role of HER2/neu, the second member of the epidermal growth factor receptor family, in breast tumors that had acquired resistance to tamoxifen in vivo. Dr. Osipo has published numerous articles, reviews, and book chapters on tamoxifen and other selective estrogen receptor modulators and downregulators. She joined Loyola University Chicago as an Assistant Professor in 2005. She is currently an Associate Professor of Pathology with tenure and the co-leader of the breast cancer program with Dr. Kathy Albain, MD. Dr. Osipo's research focuses on elucidating the role of Notch signaling in resistance to anti-estrogen and HER2-targeted therapies in breast cancer.