MET amplification

A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable. Moreover, the integration of FISH, NGS, and ddPCR provided a comprehensive assessment of MET amplification.

Combined inhibition of FGFR1 and MET significantly suppressed tumor growth in resistant cells. These findings establish MET amplification and GAB1-SHP2 signaling as central mediators of erdafitinib resistance in FGFR1-amplified MIBC and support dual FGFR1/MET targeting as a promising therapeutic strategy.

Our results further reveal that the MUC1-C-driven STAT1 inflammatory response promotes resistance of patient-derived (i) EGFR mutant NSCLC cells with MET amplification to the combination of osimertinib+MET TKIs, and (ii) EGFR(T790M/C797S) NSCLC cells to the 4th generation EGFR TKI TQB3804. Of clinical significance, we report that NSCLC cells dependent on MUC1-C for TKI resistance are druggable with an antibody-drug conjugate (M1C ADC) in vitro and in a PDX tumor model. These findings demonstrate that MUC1-C (i) is essential for TKI resistance of NSCLC cells by driving an inflammatory memory response and (ii) is a target for M1C ADC treatment of TKI-refractory NSCLCs.

Savolitinib plus osimertinib demonstrated numerically higher clinical activity versus savolitinib plus placebo in all patients and patients with higher MET biomarker cutoffs.

The study identified multiple genomic characteristics associated with primary and secondary resistance to first-line afatinib treatment in EGFR- and ERBB2-positive subpopulations.

MET amplification has been identified as a potential therapeutic target, but resistance to MET inhibitors, such as crizotinib, remains a significant challenge...Our findings suggest that acquired resistance to MET inhibitors in MET-amplified HCC may involve clonal evolution and activation of compensatory signaling pathways. These insights highlight the need for dynamic molecular surveillance and the development of strategies targeting multiple pathways to overcome resistance and improve patient outcomes.

SAC was an aggressive NSCLC subtype, with KRAS and METex14 as the most common driver mutations. Given the high prevalence of PD-L1 expression in SAC, further research on immunotherapy efficacy in this group is warranted.

These data suggest that c-Met protein OE is associated with MET mRNA expression, shows limited overlap with other MET aberrations, and may be linked to poor prognosis in NSCLC.

P1/2, N=231, Recruiting, Regeneron Pharmaceuticals | Active, not recruiting --> Recruiting

Despite the usefulness of liquid biopsy, rebiopsy should be executed whenever possible. Indeed, it remains the only tool for assessing histological transformation, which greatly impacts prognosis and treatment decisions.

Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches.

P2, N=75, Not yet recruiting, The First Affiliated Hospital, Zhejiang University School of Medicine; The First Affiliated Hospital, Zhejiang University School of Medicine