From the IFCT Predict.amm cohort of 843 consecutive patients with a treatment-naïve advanced NSCLC who were eligible for a first-line therapy, 108 NSCLC samples with high MET overexpression defined by an immunochemistry (IHC) score 3+ were tested for METex14 mutations using fragment length analysis combined with optimized targeted next generation sequencing (NGS).
In the present study we identified Echinatin (Ecn), a characteristic chalcone in licorice, which inhibited both EGFR and MET and strongly altered NSCLC cell growth.
The hepatocyte growth factor receptor mesenchymal-epithelial transition (MET) is reported to be a negative prognostic marker in EGFR-mutant NSCLC and involved in resistance to EGFR inhibitors.
Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated.
These results demonstrated how the mutated residues tune the crizotinib response and may assist kinase inhibitor development especially for ALK G1202R, analogous to the ROS1 G2302R and METG1163R mutations that are also resistant to crizotinib treatment in NSCLC.
<i>ROS1</i> rearrangements define a distinct molecular subset of non-small-cell lung cancer (NSCLC), which can be treated effectively with crizotinib, a tyrosine kinase inhibitor (TKI) targeting <i>ROS1/MET/ALK</i> rearrangements.
Although relationship between MET copy number gain and poor prognosis has been suggested in surgically resected non-small cell lung cancer, the clinical significance of MET copy number gain and protein overexpression in patients with advanced unresectable tumor is unclear.
Patients with advanced ALK receptor tyrosine kinase (ALK)-driven, ROS1-driven, or MET proto-oncogene, receptor tyrosine kinase (MET)-driven NSCLC treated with crizotinib, with or without preceding ICI therapy, were identified.
We previously developed a dual EGFR and cMET inhibitor (N19) that was able to inhibit tumor growth in nonsmall cell lung cancer models resistant to EGFR tyrosine kinase inhibitors (TKI).
Multiregion single-nucleotide polymorphism array analysis was performed on 13 early-stage resected EGFR-mutant-positive NSCLC across 59 sectors to investigate intratumoral heterogeneity of MET CNG.
This was the first NSCLC case with MET exon 14 skipping which reported the HER2 gene amplification at the time of progression during crizotinib treatment, indicating that bypass mechanisms contribute to the development of acquired resistance to MET inhibitors.
In non-small cell lung cancer (NSCLC), mesenchyme to epithelial transition (MET) protein abundance increases with disease stage and is implicated in resistance to tyrosine kinase inhibitors.
Two major mechanisms involved in resistant NSCLC (non-small cell lung cancer) include secondary acquired mutation in EGFR (epidermal growth factor receptor), that is, EGFR T790M and amplification of c-MET (hepatocyte growth factor receptor).