晚期尿路上皮癌（UC）是一种侵袭性疾病，其诱变过程尚未阐明。迫切需要靶向治疗，但从实验室到临床的道路正在缓慢进展。在这篇综述中，我们讨论了尿路上皮癌的病因学，以及 UC 候选靶向治疗的最新进展。进行了全面的数据库搜索。我们的目的是回顾 UC 基因组学和靶向治疗的最新更新。包括临床前和临床研究。我们的综述强调了在理解尿路上皮肿瘤发生的分子基础方面取得的进展，包括吸烟、化学寄生致癌物、遗传和 APOBEC3 编辑酶。我们讨论了这些因素如何导致当前 UC 的突变情况。 UC 的治疗选择仍然非常有限。然而，一些有前途的治疗方法正在开发中，以利用我们对分子靶点的了解，例如靶向成纤维细胞生长因子受体 (FGFR)、DNA 损伤修复途径和 HER2。盲目地基于其他癌症数据测试靶向疗法是不够的。需要 UC 特异性生物标志物才能针对适当人群精确使用适当的药物。迫切需要做出更多努力来了解 UC 生物学和进化论。© 2023 – 作者。由 IOS 出版社出版。

Advanced urothelial carcinoma (UC) is an aggressive disease whose mutagenic processes are yet to be elucidated. Targeted therapies are urgently needed, but the road from bench to bedside is slowly progressing. In this review, we discuss urothelial carcinoma etiology, along with the most recent advances in UC candidate targeted therapies.A comprehensive database search was performed. We aimed to review the most recent updates on UC genomics and targeted therapies. Pre-clinical as well as clinical studies were included.Our review highlights the advances in understanding the molecular basis of urothelial tumorigenesis, including smoking, chemical parasitic carcinogens, inheritance, and APOBEC3 editing enzymes. We discussed how these factors contributed to the current mutational landscape of UC. Therapeutic options for UC are still very limited. However, several promising therapeutic approaches are in development to leverage our knowledge of molecular targets, such as targeting fibroblast growth factor receptors (FGFR), DNA damage repair pathways, and HER2.Blindly testing targeted therapies based on other cancer data is not sufficient. UC-specific biomarkers are needed to precisely use the appropriate drug for the appropriate population. More efforts to understand UC biology and evolution are urgently needed.© 2023 – The authors. Published by IOS Press.