Steroid Receptors in Breast Cancer: Understanding of Molecular Function as a Basis for Effective Therapy Development.

Abstract

Simple SummaryThe knowledge we currently possess on the molecular function of steroid receptors in breast cancer is incredibly vast. New research in the field is constantly emerging, including studies focusing on potential therapeutic application of steroid receptors other than estrogen receptor which already serves as a crucial therapy target. Therefore we believe that it is necessary to regularly summarize the data on this topic. The aim of this review is to provide breast cancer researchers with a clear explanation of the complex nature of steroid receptor function, including the most up-to-date information, in order to support the effective development of future hormone therapies.Breast cancer remains one of the most important health problems worldwide. The family of steroid receptors (SRs), which comprise estrogen (ER), progesterone (PR), androgen (AR), glucocorticoid (GR) and mineralocorticoid (MR) receptors, along with a receptor for a secosteroid—vitamin D, play a crucial role in the pathogenesis of the disease. They function predominantly as nuclear receptors to regulate gene expression, however, their full spectrum of action reaches far beyond this basic mechanism. SRs are involved in a vast variety of interactions with other proteins, including extensive crosstalk with each other. How they affect the biology of a breast cell depends on such factors as post-translational modifications, expression of coregulators, or which SR isoform is predominantly synthesized in a given cellular context. Although ER has been successfully utilized as a breast cancer therapy target for years, research on therapeutic application of other SRs is still ongoing. Designing effective hormone therapies requires thorough understanding of the molecular function of the SRs. Over the past decades, huge amount of data was obtained in multiple studies exploring this field, therefore in this review we attempt to summarize the current knowledge in a comprehensive way.