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Published on: May 7, 2020
Management of Non-small Cell Lung Cancer Patients with MET Exon 14 Skipping Mutations
Caiwen Huang1, Qihua Zou1, Hui Liu2
1Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
Opinion Statement:
The MET exon 14 skipping mutation is found in approximately 3% of lung adenocarcinomas and slightly more than 2% of lung squamous cell carcinomas. In recent years, more and more evidence has shown that MET inhibitors have achieved good anti-tumor effect in patients with MET exon 14 skipping mutation, suggesting that MET exon 14 skipping mutation may be a new target for NSCLC patients. Patients with positive MET exon 14 skipping mutation are recommended to be administered MET inhibitors, and crizotinib is recommended by the NCCN guideline. Due to the presence of gene amplification, second site mutation, bypass activation, and pathological type transformation, one of the inevitable problems of targeted therapy is drug resistance. If type I MET inhibitors (crizotinib, capmatinib, tepotinib, savolitinib) drug resistance is developed, type II MET inhibitors (cabozantinib, glesatinib, merestinib) can be considered.
Insights
MET exon 14 skipping mutations are key targets in non-small cell lung cancer (NSCLC). MET inhibitors show efficacy, but resistance necessitates exploring alternative therapies like type II inhibitors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MET exon 14 skipping mutations occur in approximately 3% of lung adenocarcinomas and over 2% of lung squamous cell carcinomas.
- These mutations are increasingly recognized as actionable targets in non-small cell lung cancer (NSCLC).
- MET inhibitors have demonstrated significant anti-tumor effects in patients with these specific mutations.
Purpose of the Study:
- To highlight MET exon 14 skipping mutations as a potential therapeutic target in NSCLC.
- To discuss the efficacy of MET inhibitors and the challenge of acquired drug resistance.
- To suggest treatment strategies, including sequential use of different classes of MET inhibitors.
Main Methods:
- Review of current evidence on MET exon 14 skipping mutations in NSCLC.
- Analysis of the efficacy of MET inhibitors (type I and type II).
- Discussion of mechanisms leading to drug resistance and potential clinical management.
Main Results:
- MET inhibitors are effective against NSCLC tumors harboring MET exon 14 skipping mutations.
- Drug resistance, driven by mechanisms like gene amplification and bypass activation, is a significant clinical challenge.
- NCCN guidelines recommend crizotinib for patients with MET exon 14 skipping mutations.
Conclusions:
- MET exon 14 skipping mutation represents a promising therapeutic target for NSCLC.
- Sequential therapy with type I MET inhibitors followed by type II inhibitors may overcome acquired resistance.
- Further research into resistance mechanisms and novel therapeutic strategies is warranted.
