Rachel Schiff, PhD
Professor, Breast Center
Member, Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
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 grown in conditions that more closely mimic tissue architecture—and patient-derived models in order to study tumor growth and response to drugs. Using these innovative model systems, the team discovered a potential role of the immune system in resistance to CDK4/6 inhibitors in ER-positive breast cancer, which may be overcome by repurposing existing drugs. They also revealed a cholesterol producing pathway that has a role in anti-HER2 resistance.
Based on findings to date, the team will further expand their panel of drug-resistant breast cancer models, in particular, those that are resistant to endocrine, CDK4/6, and anti-HER2 therapies to test new drug combinations.
“ 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 had 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.
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