Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance.
Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance.
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癌症中的成纤维细胞生长因子受体：基因改变，诊断，治疗靶点和耐药机制。
DOI：
10.1038/s41416-020-01157-0
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发表时间：
2021-03
影响因子：
8.8
通讯作者：
Roychowdhury S
中科院分区：
文献类型：
--
作者：
Krook MA;Reeser JW;Ernst G;Barker H;Wilberding M;Li G;Chen HZ;Roychowdhury S
成纤维细胞生长因子受体（FGFR）通过单核苷酸变体、基因融合和拷贝数扩增在5-10%的所有人类癌症中被异常激活，尽管该频率在尿路上皮癌和肝内胆管癌中增加至10-30%。我们开始这篇综述，强调在人类癌症中发现的FGFR基因组改变的多样性，以及目前与临床级分子诊断测试的发展相关的挑战，以准确地检测患者组织和血液中的这些改变。在过去的十年中，FGFR靶向治疗的发展取得了重大进展，其中包括选择性，非选择性和共价小分子抑制剂，以及针对受体的单克隆抗体。我们描述了正在早期和随机对照临床试验中评估的抗FGFR治疗的扩展前景，例如Erdafitinib和Pemigatinib，它们分别被美国食品和药物管理局批准用于治疗FGFR 3突变的尿路上皮癌和FGFR 2融合的胆管癌。然而，尽管最初对FGFR抑制敏感，但在大多数患者中会出现导致癌症进展的获得性耐药性。这种现象强调了需要清楚地描述肿瘤内在和肿瘤外在耐药机制，以促进第二代FGFR抑制剂和靶向治疗进展以外的新型治疗策略的开发。
Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.
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DOI：
10.1158/1541-7786.mcr-18-0171
发表时间：
2018-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Childress MA;Himmelberg SM;Chen H;Deng W;Davies MA;Lovly CM
通讯作者：
Lovly CM
DOI：
10.1158/1078-0432.ccr-14-3357
发表时间：
2015-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Göke F;Franzen A;Hinz TK;Marek LA;Yoon P;Sharma R;Bode M;von Maessenhausen A;Lankat-Buttgereit B;Göke A;Golletz C;Kirsten R;Boehm D;Vogel W;Kleczko EK;Eagles JR;Hirsch FR;Van Bremen T;Bootz F;Schroeck A;Kim J;Tan AC;Jimeno A;Heasley LE;Perner S
通讯作者：
Perner S
DOI：
10.1016/s1470-2045(20)30109-1
发表时间：
2020-05
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Abou-Alfa GK;Sahai V;Hollebecque A;Vaccaro G;Melisi D;Al-Rajabi R;Paulson AS;Borad MJ;Gallinson D;Murphy AG;Oh DY;Dotan E;Catenacci DV;Van Cutsem E;Ji T;Lihou CF;Zhen H;Féliz L;Vogel A
通讯作者：
Vogel A
影响因子：
3.8
作者：
Andre, Fabrice;Cortes, Javier
通讯作者：
Cortes, Javier
影响因子：
3.3
作者：
Catenacci, Daniel V. T.;Tesfaye, Anteneh;Wainberg, Zev
通讯作者：
Wainberg, Zev