Related Experiment Video

Updated: May 16, 2025

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay
10:57

Visualizing Genetic Variants, Short Targets, and Point Mutations in the Morphological Tissue Context with an RNA In Situ Hybridization Assay

Published on: August 14, 2018

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From knowledge to action: The journey toward targeting the MET pathway via MET exon 14 skipping

Wiktoria Bogdanska1, Paul K Paik2,3

  • 1Department of Pharmacy, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

Cancer
|April 2, 2025
PubMed

Insights

Targeted therapies targeting MET alterations, including MET exon 14 skipping, have transformed non-small cell lung cancer (NSCLC) treatment. This review covers MET pathway history, pathophysiology, and evolving therapeutic strategies for NSCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The MET pathway, identified in 1984, plays a crucial role in cell survival and migration.
  • Genomic alterations in MET, such as MET exon 14 (METex14) skipping, mutations, and amplification, occur in 3%-5% of non-small cell lung cancer (NSCLC) patients.
  • These alterations lead to sustained MET receptor activation, driving tumor progression.

Purpose of the Study:

  • To review the history and pathophysiology of the MET pathway, with a focus on METex14 skipping in NSCLC.
  • To examine the evolution of diagnostic and therapeutic strategies for MET-altered NSCLC.
  • To discuss current treatments and future directions for overcoming resistance mechanisms.

Main Methods:

  • Literature review of the MET pathway, METex14 skipping, and targeted therapies in NSCLC.
  • Analysis of historical and recent research on MET alterations and their clinical implications.
  • Examination of treatment outcomes and resistance patterns associated with MET-targeted agents.

Main Results:

  • MET alterations represent a significant driver in a subset of NSCLC patients.
  • The development of next-generation sequencing has enabled the identification of these alterations.
  • Targeted therapies have shown efficacy in patients with specific MET alterations, altering the treatment landscape.

Conclusions:

  • METex14 skipping and other MET alterations are actionable targets in NSCLC.
  • Advances in understanding the MET pathway have led to novel therapeutic options.
  • Future research should focus on addressing resistance mechanisms to further improve patient outcomes.
Keywords:
METMET exon 14 skippingnext‐generation sequencingnon–small cell lung cancertargeted therapytyrosine kinase inhibitor

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