Open Access

REVIEW

Recent advances in understanding the role of sex hormone receptors in urothelial cancer

MOHAMMAD AMIN ELAHI NAJAFI^1,2,#, TAKUO MATSUKAWA^1,2,#, HIROSHI MIYAMOTO^1,2,3,*

1 Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
2 James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA
3 Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA

* Corresponding Author: HIROSHI MIYAMOTO. Email:
# Contributed equally to this work

Oncology Research 2025, 33(6), 1255-1270. https://doi.org/10.32604/or.2025.062142

Received 11 December 2024; Accepted 21 February 2025; Issue published 29 May 2025

Abstract

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.

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