Targeting Androgen/Estrogen Receptors Crosstalk in Cancer

Abstract

The actions of estrogens are mediated by estrogen receptors, ERα and ERβ. Recent genomic landscaping of ERα- and ERβ-binding sites has revealed important distinctions regarding their transcriptional activity. ERβ and its isoforms have been correlated with endocrine treatment responsiveness in breast tumors, while post-translational modifications, receptor dimerization patterns, and subcellular localization are increasingly recognized as crucial modulators in prostate carcinogenesis. Androgen receptor (AR) is essential for the development and progression of prostate cancer as well as of certain breast cancer types. The balance between the activity of these two hormone receptors and their molecular interactions in different clinical settings is influenced by several coregulators. This comprises a dynamic regulatory network enhancing or limiting the activity of AR-directed treatments in breast and prostate tumorigenesis. In this review, we discuss the molecular background regarding the therapeutic targeting of androgen/estrogen receptor crosstalk in breast and prostate cancer.

Keywords: androgen receptor; breast cancer; coregulators; estrogen receptor β; prostate cancer; transcription.