尿路上皮癌的流行病学，发病机制和雄激素受体（AR）潜在的临床作用

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

Volume: 17 Issue: 2

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

Affiliation:

关键词: 阿比特龙，雄激素，雄激素受体，雄激素阻断，膀胱癌，癌变，恩杂鲁胺，尿路上皮癌。

摘要: 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.

Cite this article as:

Maria T. Bourlon and Thomas W. Flaig , The Epidemiological, Mechanistic and Potential Clinical Role of Androgen Receptor (AR) in Urothelial Carcinoma, Current Drug Targets 2016; 17 (2) . https://dx.doi.org/10.2174/1389450116666150213120731