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成纤维细胞生长因子受体1-4基因畸变作为肺鳞状细胞癌中具有临床相关性的生物标志物

Fibroblast Growth Factor Receptor 1-4 Genetic Aberrations as Clinically Relevant Biomarkers in Squamous Cell Lung Cancer.

作者信息

Moes-Sosnowska Joanna, Chorostowska-Wynimko Joanna

机构信息

Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, Warsaw, Poland.

出版信息

Front Oncol. 2022 Mar 25;12:780650. doi: 10.3389/fonc.2022.780650. eCollection 2022.

Abstract

Fibroblast growth factor receptor (FGFR) inhibitors (FGFRis) are a potential therapeutic option for squamous non-small cell lung cancer (Sq-NSCLC). Because appropriate patient selection is needed for targeted therapy, molecular profiling is key to discovering candidate biomarker(s). Multiple FGFR aberrations are present in Sq-NSCLC tumors-alterations (mutations and fusions), amplification and mRNA/protein overexpression-but their predictive potential is unclear. Although FGFR1 amplification reliability was unsatisfactory, mRNA overexpression, mutations, and fusions are promising. However, currently their discriminatory power is insufficient, and the available clinical data are from small groups of Sq-NSCLC patients. Here, we focus on FGFR aberrations as predictive biomarkers for FGFR-targeting agents in Sq-NSCLC. Known and suggested molecular determinants of FGFRi resistance are also discussed.

摘要

成纤维细胞生长因子受体(FGFR)抑制剂(FGFRi)是鳞状非小细胞肺癌(Sq-NSCLC)的一种潜在治疗选择。由于靶向治疗需要选择合适的患者,分子谱分析是发现候选生物标志物的关键。Sq-NSCLC肿瘤中存在多种FGFR异常——改变(突变和融合)、扩增以及mRNA/蛋白质过表达——但其预测潜力尚不清楚。尽管FGFR1扩增的可靠性不尽人意,但mRNA过表达、突变和融合很有前景。然而,目前它们的鉴别能力不足,且现有的临床数据来自一小部分Sq-NSCLC患者。在此,我们聚焦于FGFR异常作为Sq-NSCLC中FGFR靶向药物的预测生物标志物。还讨论了FGFRi耐药的已知和推测分子决定因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24a2/8991910/a7ea096f4a2b/fonc-12-780650-g001.jpg

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