The Epidemiological, Mechanistic and Potential Clinical Role of Androgen Receptor (AR) in Urothelial Carcinoma

Author(s): Maria T. Bourlon, Thomas W. Flaig.

Journal Name: Current Drug Targets

Volume 17 , Issue 2 , 2016

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Abstract:

The androgen receptor (AR) is a ligand-inducible transcription factor that regulates target gene expression. Androgen signaling has been considered a putative explanation for gender differences in urothelial carcinoma (UC) incidence. In the absence of established risk factors, men still experience a threefold risk of UC as compared to women. Multiple investigations to modulate the AR have been performed with in vitro and in vivo models of UC. Down-regulation of the AR has been shown to inhibit UC growth through increased apoptosis, decreased cell proliferation, and decreased cell migration. AR activation up-regulates EGFR and HER2/neu expression contributing to UC progression. UC is more easily induced in male than female models and the incidence of chemically-induced UC is decreased by castration and the addition of estrogens; it is increased by testosterone. Epithelial to mesenchymal transition (EMT) has been postulated to be androgen-driven in UC and affects chemotherapy sensitivity. UC has not achieved the same therapeutic advances that have been seen in other tumor types in recent years. Androgen-driven events may account for some of the treatment resistance seen in this tumor type. Novel agents which disrupt androgen synthesis and/or AR signaling are in development and some (abiraterone, enzalutamide) are approved for advanced prostate cancer. Biomarker AR-driven clinical trials of highly effective anti-androgen therapy (HEAT) agents in UC present a promising picture.

Keywords: Abiraterone, androgens, androgen receptor, androgen deprivation, bladder cancer, carcinogenesis, enzalutamide, urothelial carcinoma.

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Article Details

VOLUME: 17
ISSUE: 2
Year: 2016
Page: [196 - 205]
Pages: 10
DOI: 10.2174/1389450116666150213120731
Price: $58

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