Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic
Abstract
In breast cancer the androgen receptor (AR) is more widely expressed than estrogen receptor alpha (ER) or the progesterone receptor (PR), suggesting a potential role for AR in BC. To explore the function of AR in models of the three main subtypes of breast cancer (ER positive, ER negative and Her2), we are using a new-generation AR inhibitor, enzalutamide (Enza), which impairs nuclear localization of AR. Our research seeks to determine whether Enza will be effective in breast cancer and utilize preclinical models to determine if and how it should be combined with standard treatments with the primary objective being to guide future clinical trials. In Dec 2015 Drs. Elias and Richer, demonstrate synergy between Enza and Tamoxifen or Fulvestrant in vitro and results of a Phase 1 study (NCT01597193) on pharmacokinetics and safety of Enza plus Fulvestrant in women with advanced ER disease. Regarding TNBC, we reported that AR is anti-apoptotic and facilitates anchorage independent growth and Enza decreased tumor viability in vivo. AR regulates secreted factors that support cancer stem cells and Enza significantly decreased tumor initiating capacity of TNBC in vivo. Enza administered to mice with chemotherapy greatly decreased TNBC tumor burden. These findings have guided future clinical trials with Enza in breast cancer. We report on the two trials in ER breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2020
- Accession Number
- AD1117648
Entities
People
- Jennifer K Richer
Organizations
- University of Colorado Boulder