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Kathy S. Albain, MD, FACP
Director, Breast Clinical Research Program
Co-Director, Breast Oncology Center
Director, Thoracic Oncology Program
Professor of Medicine,
Stritch School of Medicine
Loyola University Chicago
- Targeting breast cancer stem cells to prevent resistance to treatments for estrogen receptor-positive breast cancers.
- Studies are ongoing to identify the drivers of endocrine resistance for future clinical trials.
- Strategies to block survival of dormant cancer stem cells will improve patient outcomes
Endocrine (anti-hormone) therapies are effective treatment for breast cancers that rely on estrogen for growth, but resistance to these therapies often develops. Breast cancer stem cells are specialized cells that make up a small fraction of cells in a tumor but are responsible for drug resistance and recurrences. Drs. Albain and Osipo have identified a potential strategy to block cancer stem cells through a targeted approach.
Full Research Summary
Breast cancer consists of several subtypes defined by tumor biomarkers: hormone receptor-positive (ER/PR), HER2-positive, or triple negative (lacking ER, PR, and 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. Albain and Osipo 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 a potential biomarker called DAXX that may predict response to this treatment in patients.
Their ongoing studies suggest that endocrine therapy, while effective at shrinking tumors, may also promote survival of breast cancer stem cells through an interaction between Notch and DAXX. This year, the team will investigate which of these genes drives breast cancer stem cells during endocrine therapy.
With this information the team will be able to design treatments to prevent resistance to endocrine therapy. Furthermore, Notch and DAXX together could also serve as biomarkers to select patients for a future clinical trial of a combination therapy with a Notch inhibitor plus other targeted therapies.
Overall, strategies to block survival of dormant cancer stem cells will improve patient outcomes.
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.