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Updated: Mar 5, 2026
Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
MET Amplification and Response to MET Inhibitors in Stage IV Lung Adenocarcinoma
Background:
Non-small-cell lung cancers with MET amplification may respond to c-MET inhibitors.
Methods:
We examined lung adenocarcinoma patients for mutations and amplification status of epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS, MET. The clinical characteristics of patients with MET amplification and their responses to MET inhibitor therapy were studied.
Results:
Of the 76 patients analyzed, 5 were positive for c-MET gene amplification and 4 cases showed an intermediate result. For 12 patients who were EGFR positive, a c-MET analysis on secondary biopsy tissue was performed following disease progression. All 5 c-MET-positive patients were men. The age range in the study was 34-83 years. 4 of the 5 patients were started on crizotinib. 2 of these cases were positive following tyrosine kinase inhibitor therapy. 3 patients showed a response. 1 patient showed no response and was later found to have a concurrent T790M mutation.
Conclusions:
There are 2 categories of MET gene amplification in lung cancer patients, de novo and that secondary to TKI therapy. These patients can benefit from MET inhibitor therapy. Dual mechanisms of resistance, EGFR T790M mutation and c-MET amplification after TKI therapy, may suggest a poor prognosis.
Insights
MET amplification in lung cancer patients can be de novo or secondary to tyrosine kinase inhibitor (TKI) therapy. MET inhibitors show potential benefit for these patients, but dual resistance mechanisms may indicate a poor prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small-cell lung cancer (NSCLC) with MET amplification may respond to c-MET inhibitors.
- Investigating MET amplification alongside other key mutations like EGFR and ALK is crucial for personalized NSCLC treatment.
Observation:
- 5 out of 76 lung adenocarcinoma patients analyzed showed c-MET gene amplification.
- MET amplification was observed both de novo and secondary to tyrosine kinase inhibitor (TKI) therapy.
- Concurrent T790M mutation was identified in a patient with MET amplification who did not respond to therapy.
Findings:
- Patients with MET amplification, regardless of origin (de novo or TKI-induced), demonstrated potential benefit from MET inhibitor therapy.
- A significant subset of patients with MET amplification were male, with ages ranging from 34-83.
- 3 out of 5 MET-amplified patients responded to crizotinib, while one non-responder had a concurrent T790M mutation.
Implications:
- MET inhibitor therapy is a viable option for NSCLC patients with MET amplification.
- Dual resistance mechanisms, including EGFR T790M mutation and secondary MET amplification post-TKI, may predict a poorer prognosis in NSCLC.
- Understanding the distinct categories of MET amplification is key for optimizing therapeutic strategies in lung cancer.
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