Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Jan 23;10(2):29.
doi: 10.3390/cancers10020029.

Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine

Tetsuya Fujimura  1 , Kenichi Takayama  2 , Satoru Takahashi  3 , Satoshi Inoue  4
Affiliations
Review

Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine

Tetsuya Fujimura et al. Cancers (Basel). .

Abstract

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.

Keywords: androgen deprivation therapy (ADT); androgen receptor; estrogen-related receptor; personalized medicine; precision medicine; prostate cancer; selective estrogen receptor modulators (SERMs); stem cell.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Nuclear receptors associated with prostate cancer progression including androgen receptor (AR), estrogen receptor (ER), and estrogen-related receptor (ERR).
Figure 2
Figure 2
Time course of advanced prostate cancer.
See this image and copyright information in PMC

References

    1. Torre L.A., Bray F., Siegel R.L., Ferlay J., Lortet-Tieulent J., Jemal A. Global cancer statistics, 2012. CA Cancer J. Clin. 2015;65:87–108. doi: 10.3322/caac.21262. - DOI - PubMed
    1. Gillessen S., Attard G., Beer T.M., Beltran H., Bossi A., Bristow R., Carver B., Castellano D., Chung B.H., Clarke N., et al. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017. Eur. Urol. 2017;73:178–211. doi: 10.1016/j.eururo.2017.06.002. - DOI - PubMed
    1. Huggins C., Hodges C.V. Studies on prostatic cancer. I. The effect of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J. Clin. 1972;22:232–240. doi: 10.3322/canjclin.22.4.232. - DOI - PubMed
    1. Takayama K.I., Misawa A., Inoue S. Significance of microRNAs in Androgen Signaling and Prostate Cancer Progression. Cancers. 2017;9:102. doi: 10.3390/cancers9080102. - DOI - PMC - PubMed
    1. Obinata D., Takayama K., Takahashi S., Inoue S. Crosstalk of the Androgen Receptor with Transcriptional Collaborators: Potential Therapeutic Targets for Castration-Resistant Prostate Cancer. Cancers. 2017;9:22. doi: 10.3390/cancers9030022. - DOI - PMC - PubMed

LinkOut - more resources