The Role of Regulatory Proteins in Estrogen Receptor-Alpha-Mutant Breast Cancer
Abstract
Breast cancer is the most common cancer in women, and the majority of these tumors express estrogen receptor alpha (ER). Patients with ER-positive tumors are treated with hormone therapy (e.g., Tamoxifen, Femara) for years after surgery in order to block the activity of ER and prevent the spread and recurrence of their primary tumor. Hormone therapies are prescribed to approximately 150,000 new women in the US every year and have benefited many women struggling with breast cancer. Unfortunately, around 25% of women will have a tumor recurrence during their hormone therapy treatment. When tumors that do not respond to hormone therapy arise, they are very difficult to treat, and these women are unlikely to survive for another 5 years. Our hope is to identify treatments that are effective and safe for women with hormone therapy-resistant breast tumors. The proposed project aims to address the following overarching challenge defined by the Breast Cancer Research Program: Eliminate the mortality associated with metastatic breast cancer Study Design: It was recently discovered that very specific mutations in ER occur in approximately 15%-20% of hormone therapy-resistant tumors, representing approximately 50,000 women worldwide that will be diagnosed with breast cancer metastases that have these mutations during the next year. If we find a way to effectively treat these tumors, then we would prevent approximately one-eighth of breast cancer deaths in the US. Since traditional hormone therapies are relatively ineffective in patients with ER mutant tumors, we are looking at protein partners of ER as potential therapy targets. We plan to discover which protein partners work with the mutant form of ER and figure out if these partners are vulnerabilities that we can exploit in the treatment of these tumors. When possible, we will focus our efforts on trying to identify drugs that are already in clinical use with the hope of quickly moving towards a cure for patients that have breast cancer with mutations in ER. Objectives: The successful completion of this project will lead to a set of drug targets and potentially drugs that are promising candidates for safely and effectively stopping the growth and spread of metastatic breast cancer with mutations in ER. It is our hope that this preclinical work will motivate clinical trials and lead to effective and safe treatment options for patients with metastatic tumors within the next 10 years. Helping even a subset of patients who develop hormone therapy-resistant tumors would represent a major advance in the treatment of breast cancer and improve outcomes for patients faced with this terrible disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910434
Entities
People
- Jay Gertz
Organizations
- United States Army
- University of Utah