Gabriel N. Hortobagyi, MD, MACP, FASCO
To identify novel therapeutic strategies against breast cancer by blocking tumor initiation.
Breast cancer patients have varied responses to therapies with some patients experiencing a sustained benefit while others only experience side effects with little benefit. One reason for the variation in response to immune or other therapies is that breast cancer cells vary between different tumors but also within a single tumor. The latter, known as intratumor heterogeneity, is driven in part by cancer stem cells (CSCs), a small population of cells within the tumor that are highly resistant to therapy and capable of initiating new tumor formation. Since CSC-like cells contribute to tumorigenesis and immune evasion, they are thought to be drivers of breast cancer metastasis—as such, they are ideal targets for cancer treatment. Drs. Hortobagyi and Hung discovered a unique function of a common protein called human ribonuclease 1 (hRNase1) in promoting this “stemlike” quality. They will build on this discovery to develop novel strategies for treating breast cancer patients through the identification of therapeutic targets that can be used to block CSC-like characteristics.
In the last year, Drs. Hortobagyi and Hung have examined the mechanism by which the hRNase1 protein mediates breast tumor initiation. They showed that hRNase1 binds to the EphA4 receptor on breast cancer cells thereby inducing tumor initiation and CSC-like properties in these cells. Furthermore, the team discovered the precise location on both proteins by which they interact and showed that blocking this interaction can suppress tumorigenesis.
Drs. Hortobagyi and Hung will continue to investigate the targeting of the hRNase1-EphA4 axis as a promising therapeutic strategy to prevent breast cancer initiation. They will also determine whether hRNase1, which circulates in the blood, can serve as a non-invasive biomarker to stratify patients for targeted therapy.
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.
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