Baylor College of Medicine Houston, Texas
Professor, Lester & Sue Smith Breast Center, Departments of Medicine, Biochemistry and Molecular Biology Associate Director of Education, Lester & Sue Smith Breast Center, Department of Medicine
Identifying drivers of resistance and new treatment strategies 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. Osborne and Schiff 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 sophisticated 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.
In the past several years, the research group has used their growing panel of diverse and clinically relevant models to reveal several mechanisms of resistance to ER- and HER2-targeted therapies. They have also developed novel treatment combinations to overcome resistance., The group has identified key molecular factors in ER-positive breast cancer that promote endocrine resistance and metastasis, which when targeted with combination therapy could potentially overcome resistance. They have also identified potential new vulnerabilities in tumor cells resistant to CDK4/6 inhibitors that may be exploited in future studies. In HER2-positive breast cancer, they have identified multiple resistance mechanisms, including genomic aberrations in the HER2 receptors and increased levels of signaling molecules that reactivate the HER2 pathway.
The team will focus on further expanding their panel of genetically diverse models of acquired drug resistance to include current and emerging targeted agents. This includes a model of breast cancer brain metastasis resistant to anti-HER2 therapies, which will be critical for testing novel treatment strategies in this setting. They will also continue to characterize these models at the molecular and functional level and integrate them with relevant clinical datasets. Their studies will set the stage for future clinical studies to prevent or overcome resistance and will also help optimize the sequence of HER2-targeted agents in clinical practice.
Rachel Schiff, PhD 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.
2007
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