Bladder cancer is the ninth most common cancer worldwide with a striking sex-based difference in incidence. Emerging evidence indicates that the androgen receptor (AR) might promote the development, progression and recurrence of bladder cancer, contributing to the observed sex differences. Targeting androgen–AR signalling has promise as potential therapy for bladder cancer and helps to suppress progression of this disease. In addition, the identification of a new membrane AR and AR-regulated non-coding RNAs has important implications for bladder cancer treatment. The success of human clinical trials of targeted-AR therapies will help in the development of improved treatments for patients with bladder cancer.
The androgen receptor (AR) promotes bladder cancer development and progression through various molecular mechanisms, contributing to the observed sex difference in bladder cancer incidence.
The identification of the second membrane AR and AR-related non-coding RNAs provides novel therapeutic targets for bladder cancer treatment.
AR signalling can mediate resistance to cisplatin-based chemotherapy and BCG immunotherapy, providing a rationale to combine AR-targeted therapy with chemotherapy or BCG in bladder cancer.
Results of investigation into CD8+ T cell-intrinsic AR activity suggest that the roles of AR in other immune cells are worthy of investigation.
Future work addressing the interaction between anti-PD1 and anti-PDL1 immunotherapy and AR signalling in bladder cancer is needed to guide clinical therapy.
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This work was supported by the George Whipple Professorship, the National Natural Science Foundation of China (81902592, 82070785), Hunan Natural Science Foundation (2020JJ5884) and Hunan Province Young talents Program (2021RC3027). The authors thank K. Wolf for help with the manuscript preparation.
ASC-J9 was patented by the University of Rochester, the University of North Carolina and AndroScience, and then licensed to AndroScience. Both the University of Rochester and C.C. own royalties and equity in AndroScience. The other authors declare no competing interests.
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Chen, J., Huang, CP., Quan, C. et al. The androgen receptor in bladder cancer. Nat Rev Urol 20, 560–574 (2023). https://doi.org/10.1038/s41585-023-00761-y