Liewei Wang, MD, PhD
Professor of Pharmacology
Director of Pharmacogenomics Translational Program
Mayo Clinic Medical School
Identifying genetic markers that can help select the right endocrine therapy in patients with hormone receptor (HR)-positive breast cancer.
Approximately one million patients per year are diagnosed globally with estrogen receptor (ER)–positive breast cancers, which rely on estrogen to grow. This makes them a candidate for endocrine therapy, such as tamoxifen and aromatase inhibitors (AIs), which interfere with hormone signaling. While these therapies are successful in many patients, some do not experience the same benefit and side effects of these treatments can be so harsh that patients suspend therapy. Drs. Wang, Ingle, and their teams are studying how a patient’s genetic makeup can affect tolerance and response to endocrine therapy so that the most effective drugs can be selected. 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.
The team’s studies revealed that differences in the presence and alteration of certain genes can determine how a patient tolerates and responds to endocrine therapies. In addition, they found that the AI anastrozole may affect the body in unanticipated ways. Its main function is to block estrogen production by inhibiting the aromatase enzyme, but the team also found that it binds to the estrogen receptor. Depending on a patient’s estrogen levels, this could have either positive or negative effects, therefore doctors may need to adjust the therapeutic strategy for some patients on anastrozole.
The team previously identified genetic alterations in specific genes that coincide with differences in a patients’ response to AIs—they will study the function of these genes to determine if they directly affect AI response. They will also continue their exploration of anastrozole binding to the estrogen receptor and they will investigate the role of the androgen receptor, another hormone receptor, in ER-positive breast cancers.
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.
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