A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges.
A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges.
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DOI：
10.1155/2012/429213
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发表时间：
2012
影响因子：
1.4
通讯作者：
Knowles MA
中科院分区：
文献类型：
--
作者：
di Martino E;Tomlinson DC;Knowles MA
成纤维细胞生长因子（FGF）通过与其跨膜酪氨酸激酶受体（FGFR）结合并激活下游信号通路（包括RAS/MAPK、PLCγ1、PI 3 K和STAT）来协调多种细胞功能。在过去的十年中，已经清楚的是，FGF信号在高比例的膀胱肿瘤中发生了改变。FGFR 3的激活突变和/或过表达在具有低恶性潜能的尿路上皮肿瘤和低阶段和低级别尿路上皮癌（UC）中是常见的，并且在一些亚组中与较低的进展风险和较好的存活率相关。FGFR 1在UC中未发生突变，但在所有级别和阶段中频繁过表达，最近的数据表明其在尿路上皮上皮-间充质转化中发挥作用。体外和体内研究表明，FGFR抑制在FGFR依赖性膀胱癌细胞中具有细胞毒性和/或细胞生长抑制作用，目前正在临床研究中研究FGFR靶向药物治疗UC。检测常见FGFR 3突变的尿液检测也正在开发中，用于监测低级别和高阶段肿瘤以及一般人群筛查。总体而言，FGFR有望成为UC的治疗靶点、诊断和预后标志物以及早期检测和临床管理的筛查工具。
Fibroblast growth factors (FGFs) orchestrate a variety of cellular functions by binding to their transmembrane tyrosine-kinase receptors (FGFRs) and activating downstream signalling pathways, including RAS/MAPK, PLCγ1, PI3K, and STATs. In the last ten years, it has become clear that FGF signalling is altered in a high proportion of bladder tumours. Activating mutations and/or overexpression of FGFR3 are common in urothelial tumours with low malignant potential and low-stage and -grade urothelial carcinomas (UCs) and are associated with a lower risk of progression and better survival in some subgroups. FGFR1 is not mutated in UC, but overexpression is frequent in all grades and stages and recent data indicate a role in urothelial epithelial-mesenchymal transition. In vitro and in vivo studies have shown that FGFR inhibition has cytotoxic and/or cytostatic effects in FGFR-dependent bladder cancer cells and FGFR-targeted agents are currently being investigated in clinical studies for the treatment of UC. Urine-based tests detecting common FGFR3 mutations are also under development for surveillance of low-grade and -stage tumours and for general population screening. Overall, FGFRs hold promise as therapeutic targets, diagnostic and prognostic markers, and screening tools for early detection and clinical management of UC.