MET alterations in advanced non-small cell lung cancer

Curr Probl Cancer. 2024 Apr:49:101075. doi: 10.1016/j.currproblcancer.2024.101075. Epub 2024 Mar 13.

Abstract

Precision medicine has helped identify several tumor molecular aberrations to be treated with targeted therapies. These therapies showed substantial improvement in efficacy without excessive toxicity in patients with specific oncogenic drivers with advanced cancers. In metastatic lung cancers, the implementation of broad platforms for molecular tumor sequencing has helped oncology providers identify oncogenic drivers linked with better outcomes when treated upfront with targeted therapies. Mesenchymal-epithelial transition factor (MET) alterations are present in up to 60% of non-small cell lung cancer and are associated with a poor prognosis. Capmatinib and tepotinib are currently the only two approved targeted therapies by the U.S. Food and Drug Administration (FDA) for patients with MET exon 14 skipping mutation. Several agents are being developed to tackle an unmet need in patients with MET alterations. Some of these agents are being used in combination with EGFR targeted therapy to mitigate resistance to EGFR inhibitor. These agents are poised to provide new hope for these patients.

Keywords: MET amplification; MET exon 14 skipping mutation; MET overexpression; Non-small cell lung cancers (NSCLC); Precision oncology; Targeted therapy; c-MET alterations.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Molecular Targeted Therapy / methods
  • Mutation*
  • Precision Medicine / methods
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-met* / antagonists & inhibitors
  • Proto-Oncogene Proteins c-met* / genetics

Substances

  • Proto-Oncogene Proteins c-met
  • MET protein, human
  • Protein Kinase Inhibitors
  • Antineoplastic Agents