尿路上皮腫瘍におけるアンドロゲン受容体の役割 ― 膀胱癌治療へのホルモン療法応用の可能性 ―. (Japanese)

It has been well known that men have a substantially higher risk of developing bladder cancer than women. Remarkably, this sex-specific disparity has remained unchanged for many years, and its regional differences throughout the world are scarcely noticed. It is therefore difficult to explain the male dominance in the incidence of bladder cancer solely by exogenic factors, such as cigarette smoke and exposure to industrial work-related chemicals. As has been well documented in prostate cancer, emerging evidence indicates the involvement of the androgen receptor (AR) signaling pathway in the pathophysiology of urothelial cancer. In the present article, I mainly describe my own preclinical data suggesting that AR plays a critical role in urothelial tumorigenesis and tumor progression. In addition, I summarize and discuss available data suggesting that AR activation results in the induction of resistance to the conventional non-surgical treatment for bladder cancer, including intravesical BCG immunotherapy, cisplatin-based chemotherapy, and radiotherapy. Based on the current observations, the anti-tumor activity of anti-androgens as monotherapy, as well as their modulation of the efficacy of the conventional treatment as combined therapy, in patients with bladder cancer is anticipated. [ABSTRACT FROM AUTHOR]

膀胱癌が男性に約三倍多く発生することは広く知られている。世界的にみてもこの罹患率の性差に長年 大きな変化はなく，また地域差もほとんどないことから，男性優位性を喫煙や有毒化学物質等の外部要因 だけで説明するのは難しいと考えられる。一方，前立腺癌と同様に，尿路上皮腫瘍の病態生理においても アンドロゲン受容体（androgen receptor；AR）シグナルが関わることを示唆する報告が散見される。本稿 においては，AR が膀胱腫瘍の発生・再発・進展に決定的な役割を果たす可能性について，主に前臨床モデ ルを用いて行った筆者自身の研究結果を中心に概説する。加えて，膀胱癌の標準的治療であるBCG膀注療法・ シスプラチン化学療法・放射線療法に対して，AR の活性化がそれぞれの治療抵抗性を誘導している可能性 にも言及する。これらの所見から，膀胱癌患者において，抗アンドロゲン剤の単独での抗腫瘍効果や併用 療法での感受性増強効果が期待されるところである。 [ABSTRACT FROM AUTHOR]

Copyright of Nishinihon Journal of Urology is the property of West Japan Urological Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)