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Rachel Schiff, PhD
Department of Medicine, Breast Center
Baylor College of Medicine
Seeking to improve response to targeted therapies in advanced estrogen receptor-positive and HER2-positive breast cancers.
Laboratory and clinical studies are ongoing to understand resistance to endocrine and anti-HER2 therapy and develop new treatment strategies to overcome them.
These studies will lead to new clinical trials that match patients to treatments based on the molecular characteristics of each tumor.
Patients with breast cancers that have abundant levels of the estrogen receptor (ER) or the HER2 protein have several treatment options that include targeted therapies with or without chemotherapy. In spite of the success of anti-estrogen- and HER2-targeted drugs, many patients will be resistant or develop resistance to one or more of these drugs at some point during their therapy. Drs. Schiff and Osborne are conducting laboratory studies to understand what causes this resistance and to identify new treatments or new combinations that can prevent or reverse drug resistance.
Full Research Summary
Although 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 and Osborne are collaborating to develop new models of resistance that can be used in laboratory studies to identify key molecules responsible for treatment resistance and to test new treatments that will improve patient outcome.
Their BCRF-supported research suggests that drug resistance occurs because of the cooperation of compensatory and/or adaptive mechanisms that lead to the evolution of rare tumor cells with unique mutations and/or non-genetic modifications to DNA (epigenetic features). These studies have guided their discovery of several new drug combinations, including the repurposing of a promising drug that is currently being evaluated for kidney cancer.
Drs. Schiff and Osborne have also identified several resistance mechanisms to anti-HER2 therapies, which include an increase in the activity of the ER pathways, mutations in the HER2 protein itself, enriched mutations and increased levels/activity of other signaling molecules, and alterations in various components of the patient's immune system.
Over the next year, the team will continue to develop and characterize new drug-resistant preclinical models, including a laboratory model of metastatic breast cancer. They will use these, as well as clinical breast tumor samples to investigate known resistance mechanisms, identify new drivers of resistance to endocrine and anti-HER2 therapy, and develop new treatment strategies to overcome them. They hope to develop a clinical test to identify patients with HER2+ disease who can be spared chemotherapy.
Dr. Schiff is Associate 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.