{"entity":{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","aka":[],"tldr":"When lung cancer switches on the MET receptor to bypass a blocked EGFR pill.","summary":"MET amplification is a bypass form of resistance in EGFR-mutant non-small-cell lung cancer: the tumour switches on the MET receptor to keep signalling while EGFR is blocked by a pill. It occurs in a substantial minority of osimertinib-resistant tumours and is one of the escape routes targeted by amivantamab, which binds both EGFR and MET. That dual mechanism underpins the MARIPOSA combination of amivantamab and lazertinib, and the same biology motivates MET tyrosine kinase inhibitor add-on trials such as INSIGHT 2 and SAVANNAH and c-MET antibody-drug conjugates such as telisotuzumab vedotin. The term sits within acquired resistance and the receptor tyrosine kinase activation pathway, and is linked from the resistance bottleneck and the resistance-routes map.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/C-Met","links":[{"label":"Sequist et al., Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors (Science Translational Medicine 2011)","url":"https://doi.org/10.1126/scitranslmed.3002003"}],"tags":[],"related":[],"cancers":["nsclc"],"sections":[],"technologies":[],"targets":["met","egfr"],"drugs":["amivantamab","telisotuzumab-vedotin"],"companies":[],"institutions":[],"pathways":[],"terms":["resistance"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-engelman-met-amplification-gefitinib-resistance-science-2007","paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","paper-awad-met-exon-14-mutations-lung-jco-2016","paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011"],"journals":[],"dependsOn":[],"notes":["Lung cancer: the founding example of bypass resistance. MET amplification restores PI3K signalling through ERBB3 rather than through EGFR, so the EGFR inhibitor is still working and the pathway is on anyway, and it was found in 4 of 18 resistant specimens in the discovery series (Engelman 2007) and 4 of 75 in the larger rebiopsy cohort (Yu 2013). It is 2 to 3% at diagnosis (cBioPortal). There is no agreed copy-number threshold, and the treatment rule that follows from the mechanism is to add a MET inhibitor rather than to substitute one."],"category":"Resistance"},"route":"/terms/met-amplification/","neighbours":{"cancer":[{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"met-altered-nsclc","kind":"cancer","name":"MET exon 14 and MET-amplified non-small-cell lung cancer","route":"/cancers/met-altered-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"telisotuzumab-vedotin","kind":"drug","name":"Telisotuzumab vedotin","route":"/drugs/telisotuzumab-vedotin/"}],"term":[{"id":"resistance","kind":"term","name":"Drug resistance (primary and acquired)","route":"/terms/resistance/"},{"id":"met-exon-14-skipping","kind":"term","name":"MET exon 14 skipping mutation","route":"/terms/met-exon-14-skipping/"}],"paper":[{"id":"paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013","kind":"paper","name":"Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers","route":"/key-papers/paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013/"},{"id":"paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011","kind":"paper","name":"Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors","route":"/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/"},{"id":"paper-engelman-met-amplification-gefitinib-resistance-science-2007","kind":"paper","name":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","route":"/key-papers/paper-engelman-met-amplification-gefitinib-resistance-science-2007/"},{"id":"paper-awad-met-exon-14-mutations-lung-jco-2016","kind":"paper","name":"MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression","route":"/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/"}],"pairing":[{"id":"amivantamab-plus-lazertinib","kind":"pairing","name":"Amivantamab + lazertinib (first-line EGFR NSCLC)","route":"/pairings/amivantamab-plus-lazertinib/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"}],"pathway":[{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"},{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"}],"biomarker":[{"id":"met-amplification-readout","kind":"biomarker","name":"MET amplification (gene copy number)","route":"/biomarkers/met-amplification-readout/"}],"trial":[{"id":"geometry-mono-1","kind":"trial","name":"GEOMETRY mono-1","route":"/trials/geometry-mono-1/"}]}}