Liewei Wang, MD, PhD
Chair of Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics
Professor of Pharmacology
Director of Pharmacogenomics Translational Program,
Center for Individualized Medicine
Identifying genetic markers that can help select the right endocrine therapy in patients with hormone receptor-positive breast cancer.
Every year, approximately one million women globally are diagnosed 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 individuals at high risk of the disease.
The team previously identified genetic alterations in specific genes that coincide with differences in a patients’ response to AIs. They subsequently found that these alterations modify the production of other genes, and they are exploring how those genes function within tumors and under the effect of AIs. In addition, they explored how breast cancer might become resistant to the AI anastrozole. They found that anastrozole treatment prevents the destruction of a protein called fatty acid synthase (FASN), which leads to increased breast cancer cell growth. High levels of FASN are associated with poor outcomes in anastrozole-treated patients, and FASN could serve as a new therapeutic target in endocrine-resistant breast cancer.
In addition to continuing their exploration of how genetics impacts patient response to AIs, the team is exploring the role of the androgen receptor (AR), another hormone receptor, in ER-positive breast cancers. They have found an interesting relationship between the ratio of androgen of two hormone receptors, AR and ER, that may dictate how a tumor responds to AR or ER-blocking therapies. In addition, they are exploring new ways that the AR-targeting therapy, enzalutamide, may function in ER-positive tumors, and they are exploring that further.
Liewei Wang, MD, PhD 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 is the BCRF funded project in collaboration with Dr. James Ingle: the team discovered a series of biomarkers for endocrine response in breast cancer and are now 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, Chair of Pharmacology in the department of Molecular Pharmacology and Experimental Therapeutics, and Director of the Pharmacogenomics Program of the Mayo Center for Individualized Medicine.
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