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-positve and HER2-driven breast cancers.
A clinical trial is planned to test new biomarkers to predict a complete response to standard therapy.
Targeted therapies that reduce the number of breast cancer stem cells will improve treatment response and prevent metastasis.
Breast cancer is a mixture of subtypes defined by tumor biomarkers: hormone receptor-positive (ER/PR), HER2-positive, or triple negative (lacking ER, PR, 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. Osipo and Albain 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 potential biomarker that may predict response to this treatment in patients. They are continuing these studies to understand how the treatment works to promotes the destruction of breast cancer stem cells and pursue other potential biomarkers.
These biomarkers together could also be used to select patients for in a future clinical trial of combination therapy with a Notch inhibitor plus other targeted therapies and to monitor response to treatment. 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.