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[MET外显子14剪接位点突变:肺癌的新治疗机遇]

[MET exon 14 splicing sites mutations: A new therapeutic opportunity in lung cancer].

作者信息

Baldacci S, Kherrouche Z, Descarpentries C, Wislez M, Dansin E, Furlan A, Tulasne D, Cortot A B

机构信息

Université Lille, CNRS, UMR 8161-M3T, mécanismes de tumorigenèse et thérapies ciblées, Institut Pasteur de Lille, 59000 Lille, France; Service de pneumologie et oncologie thoracique, OncoLille, université de Lille, CHU de Lille, 59000 Lille, France.

Université Lille, CNRS, UMR 8161-M3T, mécanismes de tumorigenèse et thérapies ciblées, Institut Pasteur de Lille, 59000 Lille, France.

出版信息

Rev Mal Respir. 2018 Oct;35(8):796-812. doi: 10.1016/j.rmr.2018.01.011. Epub 2018 Aug 31.

Abstract

The mutations leading to MET exon 14 skipping represent a new class of molecular alterations described in various cancers. These alterations are observed in 2 to 3 % of cases of non-small cell lung cancer (NSCLC). Several cases of NSCLC carrying such alterations and achieving objective response to MET tyrosine kinase inhibitorshave recently been published. This review summarizes the molecular mechanisms responsible for MET exon 14 skipping as well as the consequences of the loss of this exon on receptor activity. We also describe the clinical characteristics of patients with METΔ14 mutations. Finally, we address the issues related to the detection of these mutations in lung cancer, and the need to anticipate resistance to MET inhibitors.

摘要

导致MET外显子14跳跃的突变代表了在各种癌症中描述的一类新的分子改变。在2%至3%的非小细胞肺癌(NSCLC)病例中观察到这些改变。最近已发表了几例携带此类改变并对MET酪氨酸激酶抑制剂产生客观反应的NSCLC病例。本综述总结了导致MET外显子14跳跃的分子机制以及该外显子缺失对受体活性的影响。我们还描述了携带METΔ14突变患者的临床特征。最后,我们讨论了与肺癌中这些突变检测相关的问题,以及预测对MET抑制剂耐药性的必要性。

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