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Rachel Schiff, PhD
Department of Medicine, Breast Center
Baylor College of Medicine
Goal: To improve response to targeted therapies in advanced estrogen receptor (ER)-positive and HER2-positive breast cancers.
Impact: Drs. Schiff and Osborne have developed a growing panel of experimental models of drug resistance and metastasis, as well as data from clinical specimens—a valuable resource to advance the understanding of the underlying causes of drug resistance. Their work could pave the way for new strategies to overcome resistance and improve patient outcomes.
What’s next: The team will continue to develop new drug-resistant preclinical models, including laboratory models of resistance to a class of drugs called CDK4/6 inhibitors and metastatic breast cancer.
Patients with breast cancers that have abundant levels of the estrogen receptor (ER) or the HER2 protein have several treatment options, which include targeted therapies with or without chemotherapy. However, many will be resistant or develop resistance to one or more of these drugs during their therapy, which leads to disease progression and metastasis. Drs. Schiff and Osborne are developing laboratory models that will help them understand the mechanisms of resistance, thus allowing them to identify new treatments or new combinations that can prevent or reverse drug resistance.
Full Research Summary
Research area: To identify key molecules responsible for breast cancer treatment resistance and to test new treatments that will improve outcomes.
Impact: 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 and Osborne are conducting laboratory and clinical studies to understand resistance to endocrine and anti-HER2 therapy and develop new treatment strategies to overcome it.
Current investigation: The team is developing new models of resistance and metastasis that can be used in laboratory studies to identify key molecules involved in treatment resistance and to test new drugs that will prevent or treat resistant/metastatic disease.
What they’ve learned so far: Drs. Schiff and Osborne have identified genetic aberrations in key proteins that alter the activity of ER and other transcription factors as a common mechanism of drug resistance and metastasis. Understanding the consequences of these genetic events and how to therapeutically target them—using their experimental models—will pave the way for new clinical strategies to overcome resistance and improve patient outcome.
What’s next: The team will continue to develop new drug-resistant preclinical models, including laboratory models of resistance to CDK4/6 therapy and metastatic breast cancer. They also plan to investigate known resistance mechanisms, identify new drivers of resistance to endocrine and anti-HER2 therapy, and develop new treatment strategies to overcome them. Finally, they hope to develop a clinical test to identify patients with HER2-positive 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.