Dear Colleagues,

Urothelial carcinoma (UC) is one of the most common malignancies worldwide. UC might arise from the upper urinary tract (UTUC) or lower urinary tract (UBUC). Of these, UTUC is relatively rare and only accounts for 5–10% of UC in Western countries while demonstrating an unusually high prevalence in certain regions. Histologically, UC can be driven by two different genetic pathways and are defined as noninvasive low-grade papillary carcinoma and high-grade non-invasive/invasive carcinomas. Somatic genetic effects play a critical role in the pathogenesis of UC. The deletion of the short arm or long arm of chromosome 9 leads to the depleted expression of CDKN2A and TSC1, respectively, and is the most frequent genetic abnormality in the urothelial tumorigenesis. The mutation of FGFR3, HRAS and PIK3CA, which are involved in the MAPK and PI3K pathways, is associated with the growth of non-invasive low-grade papillary urothelial carcinomas, while the deficiency of TP53 and retinoblastoma 1 (RB) related to cell-cycle regulation at the G1/S checkpoint are usually occurreds in high-grade in situ and invasive carcinomas. Moreover, epigenetic gene regulation has also been shown to be involved in the progression of UC. In general, hypomethylation is commonly observed in non-invasive UCs, while the highly methylated DNA was widespread in invasive UC. Although some genetic hallmarks have been disclosed for urothelial carcinogenesis, the underlying mechanism responsible for urothelial carcinoma initiation and progression remains largely unknown. Moreover, the treatment of UC is also limited by only a few targeted therapeutic agents avaible in the current stage. Accordingly, we organize this Special Issue to focus on the most updated concepts regarding molecular profiling and biological effects on novel biomarkers to understand their clinical unility and therapeutic relavance.

Prof. Dr. Chien-Feng Li
Prof. Dr. Yow Ling Shiue
Guest Editors

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• Urothelial carcinoma
• Molecular
• Pathogenesis
• Prognosis
• Predictive
• Therapy
• Theranostic