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Clodia Osipo, PhD
Associate Professor, Department of Pathology
Member, Breast Cancer Basic Science Program
Member, Cancer Immunology Research Program
Goal: To prevent resistance to treatments for estrogen receptor (ER)-positive breast cancers and triple negative breast cancers (TNBCs).
Impact: Drs. Osipo and Albain are studying a gene called DAXX that blocks breast cancer stem cells (CSCs). CSCs are the cells believed to allow tumors to survive and grow. The team is investigating how DAXX affects a patient’s response to chemotherapy and to a class of anti-cancer drugs called PARP inhibitors, used to treat some triple negative breast cancers (TNBC). Their work may reveal a way to increase DAXX expression in breast cancer cells and improve patient survival.
What’s next: The team will focus on the role of DAXX as a breast cancer suppressor and as a predictor of response to therapies in both ER-positive and triple negative disease.
While breast cancers that rely on estrogen for growth can be treated with endocrine (anti-hormone) therapy, resistance to this treatment often develops. Drs. Osipo and Albain are studying a potential biomarker called DAXX that may predict response to endocrine therapy in patients with ER-positive breast cancer. They’re also investigating high DAXX expression in TNBCs, which appears to improve response to standard chemotherapy and a class of targeted drugs called PARP inhibitors.
Full Research Summary
Research area: Developing strategies to block the survival of dormant breast cancer stem cells in order to improve patient outcomes.
Impact: Estrogen receptor (ER)-positive breast cancers are treated with endocrine therapy, such as tamoxifen or aromatase inhibitors. While these therapies are effective, resistance remains a major challenge. Drug-resistant tumors continue to grow and are more likely to spread to other organs (metastasize). Drs. Osipo and Albain have discovered several novel pathways that appear to be very important for the survival of breast cancer stem cells—cells most likely to survive anti-cancer therapies that may lie dormant for many years. Their efforts may inform the development of new strategies to block survival of dormant cancer stem cells and reduce drug resistance in ER-positive and triple negative breast cancers.
Current investigation: The team has been investigating novel cancer stem cell biomarkers that can predict the potential for response to treatment as well as resistance to therapy. Their most recent work has been focused on the biomarker DAXX.
What they’ve learned so far: Drs. Osipo and Albain have discovered that the DAXX gene is involved in the response to endocrine therapy in ER-positive breast cancer cells and that this effect is through a suppression of breast cancer stem cells. Similarly, in triple negative breast cancer cells, they found that high DAXX expression improves response to standard chemotherapy and to drugs that inhibit PARP.
What’s next: With the support of BCRF, the team will pursue three objectives:
- Understanding how DAXX inhibits breast cancer stem cells in ER-positive breast cancer.
- Determining how DAXX affects response to chemotherapy and PARP inhibitor treatment in TNBC.
- Validating these findings in patient tumor biopsies obtained at diagnosis and following treatment.
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.