Detection of MET exon 14 skipping mutations in non-small cell lung cancer: overview and community perspective

Expert Rev Anticancer Ther. 2021 Aug;21(8):877-886. doi: 10.1080/14737140.2021.1924683. Epub 2021 May 24.

Abstract

Introduction: Non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancer diagnoses in the United States, has many known driver mutations, including MET exon 14 skipping mutation (METex14). The detection of oncogenic driver mutations in NSCLC and the development of drugs to target these alterations, including METex14, has created the need for accurate and reliable testing, of which next-generation sequencing (NGS) is the gold standard. However, detection of METex14 in patients with NSCLC can be challenging due to the complex biology of METex14 and the abilities of different NGS platforms to detect METex14.Areas covered: This review provides an overview of METex14 biology, discusses the optimal platforms for the detection of METex14 in NSCLC, and provides an overview of the use of NGS in the community setting.Expert opinion: Broad molecular testing is crucial for identifying actionable oncogenic drivers in NSCLC. METex14 is a complex oncogenic driver mutation requiring carefully optimized platforms for proper detection. To identify patients eligible for targeted therapies - including therapies targeting novel oncogenic drivers, such as MET inhibitors - community oncologists need to be aware of both the use of NGS platforms and the differences in their capabilities to detect certain oncogenic drivers.

Keywords: Capmatinib; clinical decision-making; crizotinib; next-generation sequencing; savolitinib; tepotinib.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Exons
  • Humans
  • Lung Neoplasms* / genetics
  • Mutation
  • Proto-Oncogene Proteins c-met / genetics

Substances

  • Proto-Oncogene Proteins c-met