Titles and Affiliations
Professor of Medicine, Division of Hematology/Oncology
Stritch School of Medicine of Loyola University Chicago
Huizenga Family Endowed Chair in Oncology Research
Director, Breast Clinical Research and Thoracic Oncology Programs
Cardinal Bernardin Cancer Center
Research area
Developing strategies to block the survival of dormant breast cancer stem cells in order to improve patient outcomes.
Impact
Development of resistance to endocrine therapy (tamoxifen and/or aromatase inhibitors) for estrogen receptor (ER)-positive breast cancer or to chemotherapy for triple-negative breast cancer (TNBC) 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. Albain and Osipo are focused on defining the mechanisms involved in BCSC survival that may be targeted to prevent treatment resistance. With BCRF support, they have identified key pathways involved in the resistance of BCSCs to cancer treatment and demonstrated that the gene DAXX is a potent inhibitor of BCSCs. They have shown that high amounts of the DAXX gene correlate 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 to inform the development of new strategies to reduce drug resistance in ER-positive and TNBC.
Progress Thus Far
Drs. Albain and Osipo have shown that increasing DAXX levels in breast cancer cells effectively kills all breast cancer cells including BCSCs. In addition, they found high levels of the DAXX gene in ER-positive breast cancer cells inhibited resistance to endocrine therapy, and DAXX status also predicted sensitivity to chemotherapy, DNA damage response, and PARP inhibition in TNBC cells. They collected breast cancer biopsies before and after pre-surgical (neoadjuvant) endocrine therapy or chemotherapy to determine how the levels of DAXX and other cancer stem cell biomarkers are affected by neoadjuvant therapies. They found that some ER–positive breast cancer stem cells (luminal A) are more effectively killed by Notch inhibitors than others (luminal B). They will examine if different amounts of Notch receptors are responsible for the differences. This could be a new mechanism to exploit clinically to enhance killing of ER–positive cancer stem cells.
What’s next
Using the large national tumor biorepository they developed, Drs. Albain and Osipo will continue to correlate DAXX and other BCSC biomarkers with response to therapies and hope to determine which biomarkers are reliable predictors of response to endocrine therapy in ER–positive breast cancer or chemotherapy in TNBC. Screening of existing DAXX-inducing agents for their utility in preventing drug resistance and tumor relapse will also continue. They hope that their findings will enable the development of new therapies that can target BCSCs, keep DAXX levels high, prevent resistance, and ultimately cure more cancers.
Biography
Kathy S. Albain is Professor of Medicine (tenured) at Loyola University Chicago Stritch School of Medicine and is a Dean’s Senior Scholar. As a member of the Division of Hematology/Oncology, she devotes her clinical practice to patients with breast and lung cancer at Loyola’s Cardinal Bernardin Cancer Center. She is Co-leader of the Breast Cancer Program (with Clodia Osipo, PhD), Director of the Breast Clinical Research Program, Co-director of the multidisciplinary Breast Oncology Center, and Director of the Thoracic Oncology Program.
Dr. Albain is involved in national research and advisory activities pertaining to breast and lung cancers as well as cancer survivorship and special populations research. She chaired the Committee on Special Populations for SWOG, an NCI cooperative group, from its inception. This committee conducted novel research that addressed gender differences in cancer, survivorship issues, and outcome and treatment of special populations. A lay advocates program was formed under her leadership. Following SWOG reorganization, Dr. Albain served as co-chair of its Cancer Survivorship Committee. She also co-chairs an international breast cancer survivorship collaboration. Dr. Albain is a member of the SWOG working groups for breast and lung cancer. She is a member of the international Early Breast Cancer Trialists’ Collaborative Group and Steering Committee. She was a charter member of the NIH Committee on Research on Women’s Health and completed a term on the FDA Oncologic Drugs Advisory Committee (ODAC). She has over 170 publications in peer-reviewed journals and major textbooks, and is a Fellow of the American College of Physicians.
