학술논문

Targeting MET in Non-Small Cell Lung Cancer (NSCLC): A New Old Story?
Document Type
article
Source
International Journal of Molecular Sciences, Vol 24, Iss 12, p 10119 (2023)
Subject
non-small cell lung cancer (NSCLC)
mesenchymal-epithelial transition (MET)
targeted therapy
oncogene
predictive biomarkers
tyrosine kinase inhibitors (TKIs)
Biology (General)
QH301-705.5
Chemistry
QD1-999
Language
English
ISSN
1422-0067
1661-6596
Abstract
In recent years, we have seen the development and approval for clinical use of an increasing number of therapeutic agents against actionable oncogenic drivers in metastatic non-small cell lung cancer (NSCLC). Among them, selective inhibitors, including tyrosine kinase inhibitors (TKIs) and monoclonal antibodies targeting the mesenchymal–epithelial transition (MET) receptor, have been studied in patients with advanced NSCLC with MET deregulation, primarily due to exon 14 skipping mutations or MET amplification. Some MET TKIs, including capmatinib and tepotinib, have proven to be highly effective in this molecularly defined subgroup of patients and are already approved for clinical use. Other similar agents are being tested in early-stage clinical trials with promising antitumor activity. The purpose of this review is to provide an overview of MET signaling pathways, MET oncogenic alterations primarily focusing on exon 14 skipping mutations, and the laboratory techniques used to detect MET alterations. Furthermore, we will summarize the currently available clinical data and ongoing studies on MET inhibitors, as well as the mechanisms of resistance to MET TKIs and new potential strategies, including combinatorial approaches, to improve the clinical outcomes of MET exon 14-altered NSCLC patients.