Clinical and Molecular Insights on Urothelial Carcinoma

Urothelial carcinomas (UCs) are one of the most common malignant tumors worldwide, they arise from the upper urinary tracts and lower urinary tracts. Urinary bladder urothelial carcinoma (UBUC) is the most prevalent among the UCs (90%-95%). Upper tract urothelial carcinomas (UTUCs) are relatively rare compared with UBUCs and only account for 5-10% of UCs in Western countries but demonstrate an unusual high prevalence in some regions. At molecular level, UCs are driven by two different genetic pathways that form noninvasive low-grade papillary carcinoma and high-grade non-invasive/invasive carcinomasm respectively. The mutation of FGFR3, HRAS and PIK3CA involved in the MAPK and PI3K pathways are associated with the growth of non-invasive low-grade papillary urothelial carcinomas. While Deficiency of TP53 and retinoblastoma 1 (RB) related to cell cycle regulation at the G1/S checkpoint usually occurs in high-grade in situ and invasive carcinomas. Although some genetic hallmarks have been disclosed for urothelial carcinogenesis, the underlying mechanism responsible for urothelial carcinoma initiation and progression remains largely unknown. Moreover, there are relatively limited therapeutics for UCs. In spite of the development of immunotherapy and fibroblast growth factor receptors-2 and -3 targeted therapy, surgery remains to be the mainstay of early-stage UCs; chemotherapy and experimental therapies remain the therapeutic cornerstone in unresectable and metastatic UCs. Accordingly, it is mandatory to collect more molecular, translational, and clinical insights on UCs for further theranostic adjuncts.