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Liewei Wang, MD, PhD
Professor of Pharmacology
Director of Pharmacogenomics Translational Program
Mayo Clinic Medical School
Goal: To identify biomarkers that can predict which patients with estrogen receptor (ER)-positive breast cancer are most likely to benefit from anti-estrogen therapy.
Impact: Drs. Ingle and Wang are investigating how a woman’s genetic makeup affects how well she tolerates and responds to endocrine therapy with tamoxifen and aromatase inhibitors (AIs). Their findings may lead to a more personalized approach to breast cancer prevention and treatment.
What’s next: The team will study genes related to the effectiveness of tamoxifen and individual AIs. 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. Ingle and Wang 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: Identifying biomarkers for treatment response in breast cancer and developing effective targeted therapies for patients with breast cancer
Impact: Breast cancer has several different subtypes with ER+ being the most prevalent disease, while triple negative being the most aggressive disease. The treatment options are very different. For ER+ patients, even though the hormonal therapies are very effective, there are still 20% patients develop resistance and this trend does not change regardless how many years being on treatment. Therefore, it is critical to develop biomarkers that can help better individualize the therapy and select more rational combination therapies to overcome resistance.
Current investigation: Dr. Wang is using multiple omics data together with clinical phenotypes and in vitro cell and animal models to identify biomarker and study the underlying mechanisms of how these biomarkers might influence drug response and mechanisms of drug actions.
What she’s learned so far: Dr. Wang and her team has identified a series of biomarkers (SNPs/genes) that associated with hormonal treatment in breast cancer and through better mechanistic understanding, they are able to design better combination therapies based on these markers and also better understand mechanistically how these hormonal therapies might work and what are the differences among individual drug. All of these studies would help future personalized therapy of breast cancer, particular ER+ breast cancer.
What’s next: She and her colleagues aim to build more mechanistic studies to understand which subgroups of patients might benefit from these hormonal therapies and to develop new therapies in the treatment of ER+ 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.