Elahi Najafi Mohammad Amin, Matsukawa Takuo, Miyamoto Hiroshi
Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
Oncol Res. 2025 May 29;33(6):1255-1270. doi: 10.32604/or.2025.062142. eCollection 2025.
Sex hormones, including androgens and estrogens, are known to have widespread physiological actions beyond the reproductive system via binding to their cognitive receptors, members of the nuclear receptor superfamily that function as ligand-inducible transcription factors. Meanwhile, a growing body of evidence has indicated the involvement of androgen receptor, as well as estrogen receptors such as estrogen receptor-α and estrogen receptor-β, in the pathogenesis and growth of various types of malignancies, including urothelial cancer. Additionally, in bladder cancer, the activity of sex hormone receptors has been implicated in modulating sensitivity to conventional non-surgical therapy. These may clearly explain sex-related differences in the incidence and prognosis of bladder cancer. This article focuses on summarizing the recent progress on understanding the role of sex hormones and their receptors in urothelial tumorigenesis, urothelial cancer progression, and resistance to non-surgical therapy for bladder cancer. Specifically, potential downstream effectors of sex hormone receptors have been newly identified. Thus, most of previous and subsequent data have indicated that activation of the androgen receptor or estrogen receptor-β pathway is favorable for urothelial cancer, while conflicting data exist especially on estrogen receptor-α functions.
性激素，包括雄激素和雌激素，已知通过与其认知受体结合而在生殖系统之外具有广泛的生理作用，这些受体是核受体超家族的成员，作为配体诱导型转录因子发挥作用。与此同时，越来越多的证据表明雄激素受体以及雌激素受体，如雌激素受体α和雌激素受体β，参与了包括尿路上皮癌在内的各种类型恶性肿瘤的发病机制和生长过程。此外，在膀胱癌中，性激素受体的活性与调节对传统非手术治疗的敏感性有关。这些可能清楚地解释了膀胱癌发病率和预后的性别差异。本文重点总结了在理解性激素及其受体在尿路上皮肿瘤发生、尿路上皮癌进展以及膀胱癌非手术治疗耐药性方面作用的最新进展。具体而言，已新发现了性激素受体潜在的下游效应器。因此，大多数先前和后续数据表明雄激素受体或雌激素受体β途径的激活对尿路上皮癌有利，而关于雌激素受体α功能的数据存在冲突。
