Androgen deprivation
therapy (ADT) has been widely prescribed for patients with advanced
prostate cancer (PC) to control key signaling pathways via
androgen receptor (AR) and AR-collaborative transcriptional factors; however, PC gradually acquires a lethal phenotype and results in
castration-resistant PC (CRPC) during ADT. Therefore, new therapeutic strategies are required in clinical practice. In addition, ARs;
estrogen receptors (ERs; ERα and ERβ); and
estrogen-related receptors (ERRs; ERRα, ERRβ, and ERRγ) have been reported to be involved in the development or regulation of PC. Recent investigations have revealed the role of associated molecules, such as KLF5, FOXO1, PDGFA,
VEGF-A, WNT5A, TGFβ1, and
micro-RNA 135a of PC, via ERs and ERRs. Selective ER modulators (
SERMs) have been developed. Recently,
estrogen and
androgen blockade (EAB) using a combination of
toremifene and ADT has been demonstrated to improve biochemical recurrence rate in treatment-naïve bone metastatic PC. In the future, the suitability of ADT alone or EAB for individuals may be evaluated by making clinical decisions on the basis of information obtained from RT-PCR, gene-panel, or liquid biopsy to create a "
personalized medicine" or "
precision medicine". In this review, we summarize ER and ERR signaling pathways, molecular diagnosis, and
SERMs as candidates for advanced PC treatment.