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Suzanne A.W. Fuqua, PhD
Professor, Medicine and Molecular and Cellular Biology
Baylor College of Medicine
Goal: To reduce resistance to anti-estrogen therapies and prevent breast cancer metastasis.
Impact: Dr. Fuqua is studying mutations in the ER gene (ESR1) that are known to drive distant metastases and cause resistance to anti-estrogen treatment with aromatase inhibitors (AIs). Her work may inform the development of better treatment and prevention strategies for metastatic breast cancer (MBC).
What’s next: She and her team will look for patterns in the emergence of resistance in metastatic breast tumors to identify markers that may predict endocrine (anti-estrogen) drug sensitivity and lead to strategies to restore sensitivity, prevent resistance, and block the growth of metastases.
MBC occurs when breast cancer has spread to other parts of the body. At this stage, the cancer has often become resistant to many therapies. Mutations in ESR1 are commonly seen in MBC after treatment with AIs. Dr. Fuqua has discovered that these mutations not only cause tumors to be resistant to AIs but also drive the spread of breast cancer. She and her team will now study additional ways endocrine therapy resistance emerges in MBC that may help predict and ultimately prevent resistance.
Full Research Summary
Research area: Identifying mechanisms of resistance to endocrine therapy that emerge in metastatic breast cancer (MBC) to inform the development of better treatment and prevention strategies.
Impact: MBC is breast cancer that has spread to other tissues in the body. Once breast cancer has reached this stage (stage IV), it has often become resistant to many therapies. Dr. Fuqua is studying mutations in the ER gene (ESR1) that are often found in MBC and cause resistance to treatment with a class of drugs called aromatase inhibitors (AIs). Her work could lead to new, more effective ways of managing MBC.
Current research: Having discovered that ESR1 mutations are also drivers of metastasis, Dr. Fuqua and her colleagues are testing a rational drug combination to block the spread of ESR1-mutant tumors. These therapies include drugs that are already approved for use in humans and can be repurposed for use in women with MBC.
What’s next: With support from BCRF, Dr. Fuqua will look for patterns in the emergence of resistance in metastatic breast tumors, with the goal of predictng and hopefully preventing resistance, restoring endocrine sensitivity, and blocking the growth of metastases.
Dr. Fuqua has a Bachelor's degree and a Master's Degree from the University of Houston. Her PhD is in Cancer Biology from the University of Texas Graduate School of Biomedical Science. She is a Professor of Medicine and Molecular and Cellular Biology at Baylor College of Medicine. The main goal of her research is to determine the role of specific somatic mutations in estrogen receptor alpha, called K303R and Y537N, in the clinical problem of hormone resistance. Dr. Fuqua was the first to discover alternatively spliced transcriptional isoforms and somatic mutations in breast tumors. She has determined that the K303R mutation alters many aspects of hormone action, including binding to co-regulatory proteins, enhanced stability, estrogen hypersensitivity, response to tamoxifen, and resistance to the aromatase inhibitor anastrazole. Her team discovered the Y537N mutation, a constitutionally active receptor in metastatic tumors. A major goal of her laboratory is to develop novel therapeutics to target these alterations in ER alpha to restore hormone sensitivity, as well as to identify other novel mechanisms of resistance.