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


Authors: Bogdanska, W.; Paik, P. K.
Review Title: From knowledge to action: The journey toward targeting the MET pathway via MET exon 14 skipping
Abstract: Targeted therapies have radically altered the prognosis of patients with non–small cell lung cancer (NSCLC). Although the MET pathway was characterized in 1984, the treatment paradigm for patients with MET alterations has only recently changed. Genomic alterations in MET are found in 3%–5% of patients with NSCLC, and can include MET exon 14 (METex14) skipping, MET-activating mutations, and MET amplification. These alterations lead to the prolonged activation of the cellular MET receptor and downstream proliferation pathways that drive cell survival and migration. This review explores the history and pathophysiology of the MET pathway by focusing on METex14 skipping, and highlights insights gained since its discovery. Both unsuccessful and successful treatments that have emerged alongside the evolution of next-generation sequencing are examined, as well as current approved therapies and future options that target potential resistance mechanisms. © 2025 American Cancer Society.
Keywords: signal transduction; exon; genetics; mutation; exons; review; nonhuman; side effect; pathophysiology; metabolism; cell survival; carcinoma, non-small-cell lung; lung neoplasms; pathology; lung tumor; drug combination; targeted therapy; drug therapy; tyrosine kinase inhibitor; therapy; scatter factor receptor; non small cell lung cancer; met; molecularly targeted therapy; proto-oncogene proteins c-met; molecular targeted therapy; procedures; met protein, human; high throughput sequencing; next-generation sequencing; humans; human; non–small cell lung cancer; met exon 14 skipping
Journal Title: Cancer
Volume: 131
Issue: Suppl. 1
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2025-03-15
Start Page: e35782
Language: English
DOI: 10.1002/cncr.35782
PUBMED: 40172182
PROVIDER: scopus
DOI/URL:
Notes: Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Wiktoria Bogdanska -- Source: Scopus
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  1. Paul K Paik
    255 Paik