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Michael F. Press, MD, PhD
Professor of Pathology
Harold E. Lee Chair in Cancer Research
Director of Breast Cancer Analysis Lab
Keck School of Medicine
University of Southern California
Los Angeles, California
Goal: To identify biomarkers that can identify cancers with particular alterations and to predict response to targeted therapies so that more personalized treatment strategies can be used.
Impact: Dr. Press is studying both established and new breast cancer biomarkers to help guide treatment decisions for patients with breast cancer and to identify changes in genes that drive drug resistance. His work may improve patient selection for existing therapies and identify novel targets for treatments.
What’s next: He and his team will work on four separate research projects they believe will have an impact on personalized medicine for breast cancer patients. Included are investigations of a potential predictive marker of anti-estrogen treatment resistance and a potential new target for cancer therapy, among others.
Predictive markers, such as estrogen receptors (ER) and HER2, play an important role in selecting the most appropriate treatment for women with breast cancer. However, estrogen- or HER2-driven breast cancers can develop resistance to targeted therapies and continue to grow, even after initial response. Dr. Press is conducting laboratory studies to identify changes in genes that drive drug resistance and could be used as new predictive markers to select the best drug for each patient.
Full Research Summary
Research goal: Identifying changes in genes that drive drug resistance for the development of more personalized therapies for estrogen receptor (ER)-positive and HER2-positive breast cancers.
Impact: Targeted therapies have been developed to treat ER- and HER2-positive breast cancer, and these therapies have led to dramatically improved outcomes. However, some patients develop resistance to these treatments and their cancer continues to grow. Dr. Press is studying molecular alterations in breast cancers that may be potential targets for therapeutic intervention. His work is expected to have both an immediate and potentially long-term impact on personalized medicine for breast cancer patients.
Current investigation: Dr. Press’ BRCF research is on four separate research projects he believes will have an impact on personalized medicine for breast cancer patients. Included are investigations of a potential predictive marker of anti-estrogen treatment resistance and a potential new target for cancer therapy, among others.
What he’s learned so far: During the last year, Dr. Press’ team characterized several molecular genetic alterations and assessed their role in selecting breast cancer patients for various targeted therapies. These alterations include HER2/ERBB2 gene amplification and overexpression, MYST2 gene co-amplification, estrogen receptor expression, and PLK4 as a new target for breast cancer therapy. These studies have improved patient selection for existing therapies and have identified new targets for potentially new breast cancer treatments.
What’s next: In ongoing studies, Dr. Press’ team will: 1) Re-evaluate the method for determining HER2 gene amplification using information from patients with known clinical outcomes; 2) Assess the role of MYST2, a gene co-amplified along with HER2, as a potential predictive marker of anti-estrogen treatment resistance; 3) Determine whether mutations in the genes encoding PI3-kinases in tumor tissue play a role in resistance to anti-HER2 therapies; and 4) Evaluate PLK4 as a potential new target for cancer therapy.
Dr. Press is a Professor in the Department of Pathology and holds the Harold E. Lee Chair in Cancer Research at the University of Southern California’s Norris Comprehensive Cancer Center. Dr. Press is a board certified pathologist, directs the USC Breast Cancer Analysis Laboratory as well as the Central Laboratory for the Translational Research In Oncology (TRIO)/Cancer International Research Group (CIRG), and is Leader of the USC Clinical Laboratories.
His laboratory evaluates prognostic and predictive markers used in making treatment decisions for women with breast cancer. It has served as the Central Laboratory for either retrospective or prospective analyses of tissue specimens for 18 clinical trials that collectively accrued more than 13,000 patients. Dr. Press’s area of research interest is in molecular alterations of breast and gynecologic cancers, especially those that have the potential to be important in either diagnostic or therapeutic decision-making for patient management. His research has been continuously funded by research grants for more than 25 years. He is the author or co-author of more than 200 peer-reviewed publications. The most prominent area of activity for his laboratory has been in the study of the human epidermal growth factor receptor type 2 (HER2) in breast and other cancers. He published his first paper in this area in 1989 (Science 244: 707-712, 1989) and his laboratory is still actively contributing to this area as well as to the conduct of clinical trials evaluating HER2 as a target for therapy.