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靶向癌症中 FGFR 信号的进展与挑战。

Advances and challenges in targeting FGFR signalling in cancer.

机构信息

Breast Cancer Now Research Centre, Institute of Cancer Research, London SW3 6JB, UK.

Breast Unit, The Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.

出版信息

Nat Rev Cancer. 2017 May;17(5):318-332. doi: 10.1038/nrc.2017.8. Epub 2017 Mar 17.

Abstract

Fibroblast growth factors (FGFs) and their receptors (FGFRs) regulate numerous cellular processes. Deregulation of FGFR signalling is observed in a subset of many cancers, making activated FGFRs a highly promising potential therapeutic target supported by multiple preclinical studies. However, early-phase clinical trials have produced mixed results with FGFR-targeted cancer therapies, revealing substantial complexity to targeting aberrant FGFR signalling. In this Review, we discuss the increasing understanding of the differences between diverse mechanisms of oncogenic activation of FGFR, and the factors that determine response and resistance to FGFR targeting.

摘要

成纤维细胞生长因子(Fibroblast Growth Factors,FGFs)及其受体(Fibroblast Growth Factor Receptors,FGFRs)调控多种细胞过程。在许多癌症的亚群中,FGFR 信号通路失调,这使得激活的 FGFR 成为一个极具前景的治疗靶点,这一结论得到了大量临床前研究的支持。然而,针对 FGFR 的早期临床试验结果喜忧参半,这揭示了靶向异常 FGFR 信号的复杂性。在这篇综述中,我们讨论了对 FGFR 致癌激活的不同机制之间的差异以及决定 FGFR 靶向治疗反应和耐药的因素的不断深入的理解。

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