The role of androgen receptor signaling pathways in bladder cancer

Bladder cancer is estimated to be the 9th most common malignancy worldwide (1). Approximately 90% of bladder cancers have the histology of urothelial carcinoma (2). More than 70% of urothelial carcinomas of the urinary bladder (UBCs) are diagnosed as non-muscle invasive bladder cancers (NMIBCs) at initial diagnosis, while 20% to 30% of UBCs are muscle invasive bladder cancers (MIBCs) which require more comprehensive treatments (3). MIBC finally progresses into metastatic diseases despite radical surgery, and it should be treated with systemic chemotherapy (4). For patients with metastatic UBC, cisplatin-based chemotherapy, such as gemcitabine-cisplatin or MVAC regimen, has been regarded as a gold standard therapeutic option over the last few decades (4). However, response rates are poor with high resistance to these agents, and there are no approved targeted drugs for treating advanced UBC (5). Therefore, many researchers have explored novel therapeutic strategies by discovering potential target molecules, including angiogenesis-related factors, receptor tyrosine kinase, and immune checkpoint molecules, to improve the prognosis of patients with cisplatin-resistant UBC