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针对膀胱癌中的成纤维细胞生长因子受体(FGFR):是否已准备好应用于临床实践?

Targeting FGFR in bladder cancer: ready for clinical practice?

作者信息

De Keukeleire Stijn, De Maeseneer Daan, Jacobs Celine, Rottey Sylvie

机构信息

Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium.

Department of Medical Oncology, AZ Sint-Lucas, Bruges, Belgium.

出版信息

Acta Clin Belg. 2020 Feb;75(1):49-56. doi: 10.1080/17843286.2019.1685738. Epub 2019 Oct 31.

Abstract

: To give a brief literature overview of current knowledge regarding FGFR inhibition in bladder cancer.: The deeper molecular understanding of bladder urothelial carcinoma (UC) has reshaped the diagnostic and therapeutic landscape of this malignancy. Rapid technological development, including the frequent use of next-generation sequencing (NGS) in clinical practice, has boosted identification and development of potential biomarkers and targeted therapies. Genetic aberrations in the fibroblast growth factor receptor (FGFR)-pathway may drive tumorigenesis and are considered as attractive drug targets in advanced and/or metastatic UC. Several clinical trials have been performed or are ongoing to assess the safety and efficacy of (non-)selective FGFR inhibitors in patients with advanced or metatastic UC.: While non-selective FGFR inhibitors have shown limited clinical response with unacceptable toxicity, selective 'pan'-FGFR inhibitors had favourable response rates with manageable toxicity. To predict response, patients were screened for FGFR aberrations using NGS after DNA/RNA extraction of UC tissue specimen or collection of ctDNA or cfDNA.: Early clinical trials have shown promising results for targeting FGFR in advanced or metastatic UC, though these findings need to be validated in phase III trials. It seems that FGFR aberrations can be detected in ctDNA and cfDNA as efficiently as in tumour tissue, showing their potential as predictive, non-invasive liquid biomarkers.

摘要

简要概述目前关于膀胱癌中FGFR抑制的知识文献。

对膀胱尿路上皮癌(UC)更深入的分子理解重塑了这种恶性肿瘤的诊断和治疗格局。包括在临床实践中频繁使用下一代测序(NGS)在内的快速技术发展,推动了潜在生物标志物和靶向治疗的识别与开发。成纤维细胞生长因子受体(FGFR)通路中的基因异常可能驱动肿瘤发生,并被视为晚期和/或转移性UC中有吸引力的药物靶点。已经进行了多项临床试验或正在进行中,以评估(非)选择性FGFR抑制剂在晚期或转移性UC患者中的安全性和疗效。

虽然非选择性FGFR抑制剂显示出有限的临床反应且毒性不可接受,但选择性“泛”FGFR抑制剂具有良好的反应率且毒性可控。为了预测反应,在提取UC组织标本的DNA/RNA或收集ctDNA或cfDNA后,使用NGS对患者进行FGFR异常筛查。

早期临床试验显示,在晚期或转移性UC中靶向FGFR取得了有前景的结果,不过这些发现需要在III期试验中得到验证。似乎在ctDNA和cfDNA中检测FGFR异常与在肿瘤组织中一样有效,显示出它们作为预测性、非侵入性液体生物标志物的潜力。

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