Clodia Osipo, PhD
Associate Professor of Cancer Biology, Microbiology, and Immunology
Graduate Program Director, Molecular and Cellular Oncology
Co-Leader of Breast Cancer Program
Loyola University Chicago
Developing strategies to block the survival of dormant breast cancer stem cells in order to improve patient outcomes.
Development of drug resistance remains a clinical challenge. Breast cancer stem cells (BCSCs), are the tumor cells most likely to survive anti-cancer therapies and cause breast cancer recurrence many years later. Drs. Osipo and Albain are focused on defining the mechanisms involved in BCSC survival that may be targeted to prevent treatment resistance. They have identified key pathways involved in the resistance of BCSCs to cancer treatment as well as a gene called DAXX, a potent inhibitor of BCSCs. They 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 inhibitor treatment in ER-positive and TNBC cells. Further work has the potential inform the development of new strategies to reduce drug resistance in ER-positive and TNBC.
Drs. Osipo and Albain have shown that increasing DAXX levels in breast cancer cells effectively kills all breast cancer cells including BCSCs. In the past year, they found: high levels of the DAXX gene inhibited endocrine therapy-associated resistance in ER-positive breast cancer cells; and DAXX status also predicted sensitivity to chemotherapy, DNA damage response, and PARP inhibition in TNBC cells. The team has collected breast cancer biopsies before and after pre-surgical (neoadjuvant) endocrine therapy or chemotherapy and examined the levels of DAXX and other biomarkers. They are now correlating the biomarker status with response to neoadjuvant therapy.
Going forward, they will utilize a large national tumor biorepository to validate their results regarding the potential for DAXX and other biomarkers to predict response to endocrine therapy for ER-positive breast cancer and/or chemotherapy for TNBC. They will also investigate the mechanism by which DAXX turns off BCSC genes to identify strategies to target BCSCs and decrease breast cancer resistance to 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.
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