Baylor College of Medicine Houston, Texas
Professor of Medicine, Hematology and Oncology Dudley and Tina Sharp Chair for Cancer Research Founding Director Dan L. Duncan Comprehensive Cancer Center
Identifying and treating drivers of resistance in advanced estrogen receptor-positive and HER2-positive breast cancers.
While effective treatments for estrogen receptor (ER)-positive and HER2-positive breast cancers are available, many tumors are or become resistant to these therapies. Drs. Schiff, Osborne and their teams conduct laboratory and clinical studies to understand resistance to endocrine and anti-HER2 therapy and develop new treatment strategies to overcome it. They have a growing panel of experimental models of drug resistance and metastasis, as well as data from clinical specimens—valuable resources to advance the understanding of the molecular drivers of drug resistance that can be shared with the wider research community.
The team developed a variety of experimental models, including organoids—a three-dimensional sphere of cultured tumor cells that more closely mimic tissue architecture—and patient-derived models in order to study tumor growth and response to drugs. Leveraging these models, they focused on understanding mechanisms of resistance to a class of therapies known as tyrosine kinase inhibitors (TKIs) in HER2-positive breast cancer. Specifically, they explored the TKI, tucatinib (TUKYSA®) recently approved for HER2-positive breast cancer. The team found that tumors develop tucatinib resistance in a unique way, and that there may be an opportunity for a new combination therapy. They also developed a clinical test to identify patients with HER2-positive disease who can be spared chemotherapy, and those that are resistant to HER2-therapy alone, which will be soon investigated in a clinical trial.
The team recently found a new biological pathway that may be involved in resistance to endocrine and CDK4/6-targeted therapies in ER-positive breast cancer, and they will perform laboratory studies to determine what processes these pathways effect—be it tumor growth, progression, or metastatic spread. In addition, they will study DNA alterations and mutations, along with metabolic changes in HER2-positive breast cancer.
Dr. Osborne was born in St. Louis, Missouri and received his AB and his MD from the University of Missouri, both with honors. He completed his internship and residency at Johns Hopkins and followed this with three years as a Clinical Associate at the Medicine Branch of the National Cancer Institute. He was a faculty member at the University of Texas Health Science Center from 1977 until 1999 and became Chief of Medical Oncology in 1992. In 1999, Dr. Osborne moved to Baylor College of Medicine to direct a new Breast Center and in 2004 was named Director of the Dan L. Duncan Comprehensive Cancer Center at Baylor.
Dr. Osborne’s research interests have focused on the biology and treatment of breast cancer. He has published extensively on the role of growth factors in breast cancer pathogenesis, and has also investigated the mechanisms of action and resistance to ER and HER2 targeted therapies in breast cancer. Dr. Osborne currently directs the Baylor Breast Cancer Specialized Program of Research Excellence Grant. Dr. Osborne has authored more than 400 manuscripts dealing with the biology and treatment of breast cancer.
2002
The Macy's Award
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