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Liewei Wang, MD, PhD
Professor of Pharmacology
Director of Pharmacogenomics Translational Program
Mayo Clinic Medical School
Goal: To identify genetic markers that can help select the right anti-estrogen therapy and reduce the risk of recurrence in women with estrogen receptor (ER)-positive breast cancer.
Impact: Tamoxifen and aromatase inhibitors are the most effective treatments for breast cancers that depend on estrogen (called ER-positive) to grow—about 70 percent of breast cancers. Unfortunately, many women will still succumb to the disease. Drs. Wang and Ingle are focused on identifying factors, including a woman’s genetic make-up, to individualize the selection of therapy. The potential impact of this research is enormous given that about one million women per year are diagnosed globally with ER-positive breast cancers that make them candidates for endocrine therapy.
What’s next: The team will continue studies aimed at individualizing endocrine therapy by studying genes related to the effectiveness of tamoxifen and aromatase inhibitors. They will also continue to investigate how anastrozole (an AI) interacts with the estrogen receptor and how the estrogen receptor and androgen receptor (AR) work together to determine how patients respond to AR-directed therapy.
Most breast cancers require estrogen to grow. They are treated with endocrine (anti-estrogen) therapy with tamoxifen and a class of drugs called aromatase inhibitors (AIs). However, response to these therapies varies; some women experience more side effects than others and may stop treatment. Drs. Wang and Ingle are studying how a woman’s genetic makeup can affect her tolerance and response to endocrine therapy so that the most effective drugs can be selected for each patient.
Full Research Summary
Research Area: Understanding the mechanisms by which a patient’s genetic makeup affects the action of anti-estrogen therapy.
Impact: Endocrine (anti-estrogen) therapies, such as tamoxifen and aromatase inhibitors, are the most important treatment for breast cancers that rely on estrogen to grow. These so-called estrogen receptor (ER)-positive breast cancers make up the majority of all breast cancers. However, not all patients experience the same benefit from endocrine therapy, and some find the treatment side effects intolerable. Drs. Wang and Ingle are conducting studies to investigate how a patient’s genetic makeup can be used to individualize the selection of endocrine therapies and other treatments. Their findings will ultimately enable doctors to select the best therapy to prevent breast cancer or breast cancer recurrence in women at high risk of the disease.
Current investigation: Drs. Wang and Ingle are performing multiple studies to determine the impact of a woman’s genetic makeup on the effects of endocrine therapy. In particular, they are studying the genes related to tamoxifen and aromatase inhibitor function, the ZNF423 and MIR2052HG genes, respectively.
What they’ve learned so far: Their studies have shown that differences in the expression of certain genes can determine how a woman tolerates and responds to tamoxifen and AIs. They have also identified that different genes are associated with the efficacy of the AI anastrozole compared to other AIs and found a novel mechanism of anastrozole in the treatment of ER-positive breast cancer.
What’s next: The team will continue their studies to understand the interactions of genetic variations and response to anti-estrogen-based therapies. They will characterize pathways regulated by anastrozole and identify drugs that could improve the efficacy of anastrozole and characterize the roles of the estrogen and androgen receptors in response to androgen -directed therapy in breast cancer.
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.