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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: When breast cancer spreads to other tissues, it often loses its sensitivity to anti-cancer drugs. For the most common type of breast cancer, called estrogen receptor (ER)-positive, mutations in the ESR1 gene are a cause of resistance to anti-estrogen therapies called aromatase inhibitors (AI) and promote metastasis. Dr. Fuqua’s research is focused on finding ways to counter the effect of mutated ESR1 in order to improve treatment and prevention strategies for metastatic breast cancer (MBC).
What’s next: She and her team will target a major weakness they recently discovered in ESR1-mutant breast tumors.
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 and is incurable. 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 are now developing a new way to target ESR1-mutant MBC in combination with AIs to ultimately improve the treatment of MBC.
Full Research Summary
Research goal: Identifying mechanisms of resistance to endocrine therapy that emerge in metastatic breast cancer (MBC) and targeting them to make metastatic tumors more susceptible to treatments.
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 how to exploit 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 ER-positive MBC.
Current investigation: 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 patients with MBC.
What she’s learned so far: Dr. Fuqua and her team have identified an exciting vulnerability in metastatic breast tumors that harbor ESR1 mutations. These tumors are growing at a hyper rate, and because of this they experience what is called “replication stress” due to rapid cellular cycling. The team can attack this vulnerability with existing drugs, using them in novel combinations. Dr. Fuqua believes that this approach may also restore tumor sensitivity to AIs and be a promising new therapeutic combination to treat MBC.
What’s next: With support from BCRF, Dr. Fuqua will target replication stress using cell cycle checkpoint inhibitors in combination with AIs and continue to study mechanisms of resistance and drivers of metastasis.
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.