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Clodia Osipo, PhD
Associate Professor of Cancer Biology and Microbiology and Immunology
Graduate Program Director: Molecular and Cellular Oncology, Co-Leader of Breast Cancer Program
Loyola University Chicago
Goal: To prevent resistance to treatments for estrogen receptor (ER)-positive and triple-negative breast cancer (TNBC).
Impact: Breast cancer stem cells (BCSCs) are the cells believed to allow breast cancer tumors to resist treatment. Drs. Osipo and Albain are studying a gene called DAXX that blocks BCSCs. The team is investigating how DAXX affects a patient’s response to chemotherapy, as well as other cancer fighting drugs, including PARP-inhibitors that 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 are also investigating high DAXX expression in TNBC, 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—the cells most likely to survive anti-cancer therapies and cause breast cancer recurrence many years later. 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 cancer (TNBC).
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 identified DAXX and Notch as key pathways in the resistance of BCSCs to cancer treatment. Their studies have shown that high amounts of the DAXX gene correlates with a reduction in the number of BCSCs and a better response to endocrine therapy, standard chemotherapy, and PARP-inhibitors in ER-positive and triple negative breast cancer cells. In addition, they have shown that phytoestrogens found in some food products increase the expression of the DAXX gene resulting in a decrease in BCSCs.
What’s next: Drs. Osipo and Albain will now examine breast cancer tissue before and after pre-surgical therapy to determine if the levels of DAXX and other biomarkers predict long term survival in estrogen receptor-positive disease. They will also continue their studies to determine how DAXX can regulate and predict the tumor’s response to chemotherapy and/or PARP-inhibitors in ER-positive and TNBC.
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.