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Gabriel N. Hortobagyi, MD, FACP, 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: Drs. Hortobagyi and his MD Anderson colleagues have found that the anti-diabetes drug metformin can be given to patients to enhance the effectiveness of immunotherapy. They have also identified an enzyme that may serve as a biomarker to predict resistance to a specific type of immunotherapy (anti PD-1 and anti PD-L1 immune checkpoint therapy).
What’s next: The team will finalize their proposed study of the mechanisms of resistance to anti PD-1 and anti PD-L1 therapies, which they hope will lead to new treatment strategies for TNBC.
TNBC is an aggressive form of breast cancer that is challenging to treat and is more likely to spread and recur. Immunotherapies have shown some benefit in patients with TNBC, but most receive very little benefit and may suffer severe side effects. Dr. Hortobagyi's team is investigating the causes of resistance to PD-L1/PD-1 immune checkpoint therapy, which will allow them to develop effective combination therapies to overcome resistance.
Full Research Summary
Research area: Identifying new strategies for treatment of triple-negative breast cancer (TNBC), which is more aggressive and difficult to treat compared to other types of breast cancer.
Impact: While targeted therapy has been successful in treating several types of breast cancer, it has failed to improve outcomes in those with TNBC. Immunotherapies have shown benefit for some patients in clinical trials, but response is low, and the drugs can cause severe side effects. Dr. Hortobagyi's team is investigating the causes of resistance to these therapies, which may lead to alternative approaches to improving response.
Current research: The work been focused on enhancing response to anti-PD-1 and anti-PDL1 therapies, which belong to a class of drugs called immune checkpoint inhibitors. Connections between PD-L1 and its sister molecule, PD1, allow cancer cells to go undetected by the immune system.
What they’ve learned so far: Metformin—a commonly used drug to treat type 2 diabetes that has been reported to possess anti-tumor activity—has the potential to increase the efficacy of immunotherapy. The research team identified a biomarker that may be used to predict resistance to anti-PD-1/PD-L1 treatment.
What’s next: The team will study a monoclonal antibody they developed that targets glycosylated PD-L1. Glycosylation is a process that attaches portions of sugar molecules to a protein, providing it fuel to grow and spread. Result thus far suggest that targeting glycosylated PD-L1 may be a potential strategy to enhance immune checkpoint therapy in TNBC.
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 1000 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 currently the Chair of the Southwest Oncology Group Breast Committee and a member of the Scientific Advisory Board of The Breast Cancer Research Foundation.