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Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic

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Technical Report,15 Aug 2014,14 Aug 2015

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The Regents of the University of Colorado Aurora

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In breast cancers, the androgen receptor AR is more widely expressed than estrogen receptor alpha ER or the progesterone receptor PR 1, which are used as therapeutic targets and biomarkers, 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 anew-generation AR inhibitor, enzalutamide, which impairs nuclear localization of AR. This is a very different mode of action than previous generation anti-androgens such as bicalutamide Casodex, which is a competitive inhibitor of endogenous androgens that allows ligand-mediated nuclear localization of AR. Enzalutamide has shown success in the clinic in patients with late stage prostate cancer. The research in this proposal seeks to determine whether inhibition of AR with enzalutamide will be effective in breast cancer and utilize preclinical models of the three main subtypes of breast cancer to determine if and how it should be combined with currently used standard of care treatments in the three main types of breast cancer, with the primary objectives of the research being to guide the design of future clinical trials with enzalutamide.

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