Abstract

The identification of mutations in FGFR3 in bladder tumors in 1999 [1] led to major interest in this receptor and during the subsequent 20 years much has been learnt about the mutational profiles found in bladder cancer, the phenotypes associated with these and the potential of this mutated protein as a target for therapy. Based on mutational and expression data, it is estimated that >80% of non-muscle-invasive bladder cancers (NMIBC) and ∼40% of muscle-invasive bladder cancers (MIBC) have upregulated FGFR3 signalling, and these frequencies are likely to be even higher if alternative splicing of the receptor, expression of ligands and changes in regulatory mechanisms are taken into account. Major efforts by the pharmaceutical industry have led to development of a range of agents targeting FGFR3 and other FGF receptors. Several of these have entered clinical trials, and some have presented very encouraging early results in advanced bladder cancer. Recent reviews have summarised the drugs and related clinical trials in this area [2– 5]. This review will summarise what is known about the effects of FGFR3 and its mutant forms in normal urothelium and bladder tumors, will suggest when and how this protein contributes to urothelial cancer pathogenesis and will highlight areas that may benefit from further study.

中文翻译：

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FGFR3 –膀胱癌发病机制的重要参与者？

摘要

FGFR3突变的鉴定在1999年的膀胱肿瘤中[1]引起了人们对该受体的极大兴趣，在随后的20年中，人们对膀胱癌中发现的突变谱，与之相关的表型以及该突变蛋白作为靶标的潜力的了解很多。治疗。根据突变和表达数据，估计> 80％的非肌肉浸润性膀胱癌（NMIBC）和约40％的肌肉浸润性膀胱癌（MIBC）具有上调的FGFR3信号传导，这些频率很可能是如果考虑受体的可变剪接，配体的表达和调节机制的改变，则更高。制药业的主要努力已导致开发出一系列靶向FGFR3和其他FGF受体的药物。其中一些已经进入临床试验，一些已经在晚期膀胱癌中表现出令人鼓舞的早期结果。最近的评论总结了该领域的药物和相关的临床试验[2-5]。这篇综述将总结关于FGFR3及其突变体形式在正常尿路上皮和膀胱肿瘤中的作用的已知信息，将提示何时以及如何该蛋白促进尿路上皮癌的发病机理，并将重点介绍可能需要进一步研究的领域。