Rachel Schiff, PhD
Professor and Breast Center and Member,
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.
This shareable and valuable resource enables more studies to better understand mechanisms of resistance and novel therapeutic strategies to overcome them. – Dr. Schiff
Dr. Schiff is Professor at the Baylor College of Medicine, Sue & Lester Smith Breast Center and the Departments of Medicine and Molecular and Cellular Biology. She is an internationally recognized expert in breast cancer translational research and in preclinical therapeutic models, especially concerning endocrine, HER2, and additional targeted therapies. Dr. Schiff received her PhD in 1992 from Hebrew University Hadassah Medical School in Jerusalem and completed her post-doctoral fellowship at University of Texas Health Science Center, San Antonio. She joined Baylor College of Medicine in 1999 as a faculty member of the Sue & Lester Smith Breast Center.
Dr. Schiff's research focuses on understanding key signaling pathways in breast cancer and on identifying therapeutic strategies to overcome them. Major interests include molecular aspects of estrogen receptor (ER) and HER2 action in breast cancer, the crosstalk between the ER signaling network and growth factor receptor and cellular kinase pathways, the role of ER co-regulators in breast cancer development and progression, mechanisms of resistance to targeted therapies, and the identification of biomarker and signatures of hormonal and anti-HER2 therapy resistance for therapeutic interventions. Dr. Schiff's research is partly supported by grants from the National Cancer Institute, BCRF, Susan G. Komen for the Cure, and the Department of Defense Breast Cancer Research Program.
The Macy's Award
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