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Liewei Wang, MD, PhD
Professor of Pharmacology
Associate Director, Pharmacogenomics Translational Program
Mayo Clinic Medical School
- Seeking to identify biomarkers that can predict who is most likely to benefit from anti-estrogen prevention therapy.
- Studies are ongoing to explore potential genetic markers related to effectiveness of tamoxifen and aromatase inhibitors.
- This work may lead to a more personalized approach to prevention that is based on a woman's genetic makeup.
The majority of breast cancers rely on the hormone estrogen for growth. Anti-estrogen therapies are effective at both treating and preventing this kind of breast cancer- called estrogen receptor (ER)-positive. Side effects from hormonal therapy, however, cause many women to stop taking it. Drs. Wang and Ingle are conducting studies to understand how a woman’s genetic makeup affects her response to anti-hormone therapy. They hope to identify genetic markers that can help select the best preventive therapy for each woman.
Full Research Summary
Tamoxifen and raloxifene belong to a class of anti-estrogen drugs called SERMs and are effective agents for the chemoprevention of breast cancer. However, many women at high risk for breast cancer will not take these drugs due to the potential for toxicity. Women differ in their genetic make-up, and this variability can determine how a woman tolerates and responds to drugs such as tamoxifen and aromatase inhibitors.
The focus of Drs. Wang and Ingle’s research is to identify biomarkers that can predict who is most likely to benefit from SERM prevention therapy and aromatase inhibitors. They have identified two genetic markers that appear to be associated with response to SERM treatment. The same genes are involved in regulation of the BRCA genes, and so they may also be important in selecting patients for PARP inhibitor therapy, a therapy that has been approved to treat advanced BRCA-related breast and ovarian cancers.
These findings indicate that, for the first time, breast cancer prevention therapy may be able to be "personalized" by using genetic biomarkers. The team will continue to explore the genetic differences related to effectiveness of tamoxifen and aromatase inhibitors.
Their ultimate goal is to establish the genetic basis for selecting the best endocrine therapy treatment for a given woman, either to prevent breast cancer when she is at high risk or to prevent recurrence when she has already been diagnosed.
Dr. Liewei Wang received her medical degree from FuDan University Medical School, Shanghai, followed by a PhD degree in Pharmacology from the Mayo Clinic. She trained in a leading national center for pharmacogenomics (PGx) research. Currently Dr. Wang is Professor of Pharmacology at Mayo where she has developed a research program focused on the use of genomic technology joined with a cell-based model system and clinical samples to study mechanisms of cancer biology and drug response. As Co-PI of the Mayo-NIH Pharmacogenomics Research Network (PGRN) grant for the past decade she has led PGx functional genomic studies of breast cancer designed to identify and understand biomarkers for response to endocrine and chemotherapy of breast cancer. Among those studies are the BCRF funded project in collaboration with Dr. James Ingle, in which her group has discovered a series biomarkers for endocrine response in breast cancer and they are studying the basic mechanisms associated with these biomarkers to help design better individualized endocrine therapy. She also leads a Mayo program developing new experimental models for breast and prostate cancer. Dr. Wang has published extensively in high impact journals and has received the Astellas Award from Astellas Foundation and the 2016 Leon Goldberg Early Investigator Award from the American Society for Clinical Pharmacology and Therapeutics. Dr. Wang is a member of the Mayo-NCI Comprehensive Cancer Center and Associate Director of the Pharmacogenomics Program of the Mayo Center for Individualized Medicine.