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Gabriel N. Hortobagyi, MD, MACP, FASCO
Professor, Department of Breast Medical Oncology
University of Texas MD Anderson Cancer Center
University of Texas MD Anderson Cancer Center
Member, BCRF Scientific Advisory Board
Goal: To improve outcomes in patients with triple-negative breast cancer (TNBC) by enhancing response to existing therapies and developing new ones.
Impact: Encouraging results have been seen with immunotherapy using anti-PD1 monoclonal antibodies, however, the response rate to this therapy is only about 15-20 percent. Drs. Hortobagyi and Hung are developing better strategies for the treatment of breast cancer patients and extending their studies to identify other therapeutic targets that to block the cancer stem cell-like characteristics of aggressive breast cancer .
What’s next: The team will finalize their studies on the mechanisms of resistance to anti PD-1 therapy and expand their research to develop novel therapeutic strategies aimed at the stem cell capabilities of aggressive breast cancers, particularly TNBC.
TNBC is an aggressive form of breast cancer that is challenging to treat and is more likely to spread and recur. Part of its aggressive nature is due to cancer stem cell-like characteristics. Cancer stem cells—sometime called tumor initiating cells—are thought to be drivers of breast cancer metastasis. Drs. Hortobagyi and Hung have identified a novel function of common protein in promoting cancer stem cell-ness. They are conducting studies to confirm these findings and determine whether this protein, which circulates in the blood, may be used as a biomarker for identifying patients for targeted therapies.
Full Research Summary
Research area: Developing novel therapeutic strategies for the treatment of triple-negative breast cancer (TNBC).
Impact: Triple-negative breast cancer is an aggressive form of breast cancer with limited treatment options. Targeted therapies such as the immune checkpoint (anti-PD-L1) therapies, have had limited success in TNBC. Some patients experience a sustained benefit while others only experience side effects. One reason for the variation in response to immune or other therapies is that TNBC is a very heterogeneous disease–not only is there variability between different TNBC tumors but also within a single TNBC tumor. This intratumor heterogeneity is driven in part by cancer stem cells—a small population of cells within the tumor that are highly resistant to therapy and capable of forming new tumors. In the course of their BCRF-research, Drs. Hortobagyi and Hung discovered a unique function of a common protein called human ribonuclease 1 (hRNaseA) in promoting this stemlike quality.
Current investigation: In the coming year, Drs. Hortobagyi and Hung are pursuing studies in human ribonuclease 1 (hRNase1), which their preliminary finding show is associated with poorer survival in several subtypes of breast cancers. They will investigate the role of hRNase1 in the initiation of breast cancer and examine its potential as a non-invasive serum biomarker for breast cancer. These studies will lead to the identification of a novel therapeutic strategy against breast cancer aimed at decreasing the tumor-initiating capabilities.
Dr. Gabriel Hortobagyi is an internationally recognized expert in clinical and translational research of breast cancer. He is Professor and the Chair Emeritus of the Department of Breast Medical Oncology at the MD Anderson Cancer Center. He was Hematology/Oncology Training Program Director at MDACC for many years and continues as member of the educational faculty.
He is Past President of the American Society of Clinical Oncology (ASCO) and is one of the world's leading authorities on the management of breast cancer. Dr. Hortobagyi is recipient of numerous awards. He has over 1100 full-length publications in peer-reviewed journals, and over 140 book chapters to his credit. Dr. Hortobagyi served on various task forces and committees of the American Society of Clinical Oncology, served on the Board of Directors, and in 2005 was elected President. He served as President of the International Society of Senology, as a member of the U.S. National Committee for the International Union Against Cancer, the National Cancer Institute’s Breast Cancer Progress Review Group, and the Integration Panel of the Breast Cancer Research Program of the Department of Defense, chaired the Steering Committee of the Breast Health Global Initiative, the Health Advisory Board of the Susan G. Komen Breast Cancer Foundation and the NCI’s Operational Efficiency Working Group. Dr. Hortobagyi is Immediate Past Chair of the Southwest Oncology Group Breast Committee and a member of the Scientific Advisory Board of The Breast Cancer Research Foundation.