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

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

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.

Keywords: Cancer du poumon; Lung cancer; MET; Récepteur tyrosine kinase; Targeted-therapies; Thérapie ciblées; Tyrosine kinase receptor.

Publication types

  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Exons
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / therapy*
  • Molecular Targeted Therapy* / methods
  • Molecular Targeted Therapy* / trends
  • Mutation*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met / genetics*
  • RNA Splice Sites / genetics*

Substances

  • Protein Kinase Inhibitors
  • RNA Splice Sites
  • MET protein, human
  • Proto-Oncogene Proteins c-met