MET encodes a receptor tyrosine kinase; oncogenic activation in NSCLC most often arises from splice-site alterations causing exon 14 skipping, rather than from point mutations in the kinase domain.
MET exon 14 skipping alterations are the primary actionable finding; MET amplification is a distinct, separately assessed mechanism of activation and of acquired resistance to EGFR TKIs.
Clinical significance
NSCLC with MET exon 14 skipping alterations is eligible for MET tyrosine kinase inhibitor therapy.
fda — FDA-approved product labeling for MET TKIs
FDA-approved treatments
- Tabrecta (capmatinib) — Metastatic NSCLC with MET exon 14 skipping alterations, as detected by an FDA-approved test [fda]
- Tepmetko (tepotinib) — Metastatic NSCLC with MET exon 14 skipping alterations [fda]
Prevalence
MET exon 14 skipping alterations occur in approximately 3%-4% of NSCLC, more common in older patients and those with sarcomatoid histology. [fda]
Tests / detection method
NGS (RNA-based assays preferred for splice variants)
Therapeutic pipeline
- MET-directed antibody-drug conjugates (MET amplification) [fda]
Recent news for MET
PubMed Central · Aug 12, 2026
1D228 Attenuates Sorafenib Resistance in Renal Cell Carcinoma Models by Dual Targeting c-Met and AXL.
Read at PubMed CentralPubMed Central · Aug 11, 2026
C-MET tyrosine kinase receptor: mechanisms, clinical applications and future perspectives in cancer therapy.
Read at PubMed CentralPubMed Central · Jun 9, 2026
Consistency of c-Met protein overexpression over time in patients with non-squamous non-small cell lung cancer.
Read at PubMed Central