Molecular Modeling of Estrogen Receptor Alpha Mutated Breast Cancer to Guide New Therapeutic Strategies
Technical Report,30 Sep 2016,29 Sep 2017
Regents of the University of Colorado Aurora United States
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The expression of estrogen receptor alpha ER is assayed in every breast cancer biopsy at the time of diagnosis with the majority of tumors 70 expressing ER. Hormone therapy is given to patients with ER expressing tumors for years after surgical resection to block the creation of estrogens or the activity of ER. Unfortunately, many patients develop hormone therapy resistant tumors and once metastatic disease is found in these patients, the outlook is poor with the median survival time of slightly over one year. The recent discovery of mutations in the ligand-binding domain LBD of ER in 10-40 of metastatic hormone therapy resistant breast tumors suggests that these mutations may be a common mechanism leading to resistance. There is a need to understand the molecular changes that arise due to ER LBD mutations and find effective treatments for patients whose tumors harbor these mutations. We have two main goals for this project. The first goal is to characterize the molecular consequences that are specific to ER LBD mutations found in metastatic breast cancer. The second goal of the project is to identify promising targeted therapies for patients with hormone therapy resistant breast tumors that harbor ER LBD mutations.
- Medicine and Medical Research