{"entity":{"id":"met","kind":"target","name":"MET","aka":[],"tldr":"A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.","summary":"MET exon 14 skipping (~3% NSCLC) responds to capmatinib and tepotinib. MET amplification drives resistance to EGFR inhibitors; amivantamab (EGFR×MET) and MET ADCs (telisotuzumab vedotin, Emrelis, approved 2025 in c-Met overexpressing NSCLC) address it. c-MET×EGFR bispecific ADCs (tilatamig samrotecan) lead the bsADC field.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/C-Met","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/C-Met"}],"tags":["driver","kinase","adc-target"],"related":["met-ex14","met-amplification-readout","met-overexpression"],"cancers":["nsclc","gastric","rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["guardant360-cdx","zanzalintinib","lam561","bezuclastinib","al2846","hs-20117","mcla-129","tqb6411","tqb2922","hdm2017","js111"],"companies":["imagene-ai","lucence","mythic-therapeutics"],"institutions":[],"pathways":["ras-mapk","pi3k-akt-mtor","hepatocellular-carcinoma-signalling","nsclc-signalling","renal-cell-carcinoma-signalling"],"terms":["met-exon-14-skipping","met-amplification"],"trials":["nct07439094","nct06669117"],"people":[],"bottlenecks":[],"keyPapers":["paper-awad-met-exon-14-mutations-lung-jco-2016","paper-tcga-lung-adenocarcinoma-nature-2014","paper-frampton-met-exon-14-cancer-discov-2015","paper-lindeman-lung-molecular-testing-guideline-jto-2018","paper-kris-lung-cancer-mutation-consortium-jama-2014","paper-engelman-met-amplification-gefitinib-resistance-science-2007"],"journals":[],"dependsOn":[],"notes":["Lung cancer: two separate biomarkers in one gene. Exon 14 skipping, 2 to 4% of adenocarcinomas, is a binary sequencing call and a first-line target, and it is the alteration a coding-exon panel most easily misses because the variants sit in the flanking introns (Frampton 2015, Awad 2016). Its patients are older (median 72.5 years), more often women (68%) and often never smokers (36%). MET amplification, 2 to 3%, is a continuous copy-number call with no agreed threshold, is more often acquired under EGFR blockade than present at diagnosis, and was the first bypass mechanism described, in 4 of 18 resistant specimens (Engelman 2007). Concurrent amplification of a mutated allele predicts the deepest responses (Awad 2016)."],"symbol":"MET","role":[],"sources":[],"specificity":"tumour-associated","distribution":"few-types","specificityNote":"Tumour-associated overexpression or amplification: 2 of 3 label readouts filed under it score protein level or gene copies (c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells), MET amplification (gene copy number)), so the medicines rely on the tumour carrying more of it than normal tissue; 1 measure a variant (MET exon 14 skipping mutation). HPA MET: RNA tissue enhanced (liver 40 nTPM); high antibody staining in 8 normal tissues; highest cancer staining colorectal cancer (7 of 12 high). Distribution: 3 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lung cancer (all types), Gastric & gastro-oesophageal junction cancer, Renal cell carcinoma); approvals of single-target medicines aimed at it also list Brain and spinal cord tumours (all types), not counted; Open Targets associates it with 7 specific cancer types at or above 0.5 (papillary renal cell carcinoma, hereditary papillary renal cell carcinoma, hepatocellular carcinoma, renal cell carcinoma, non-small cell lung carcinoma, medullary thyroid gland carcinoma and more). (Rule 3 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells) label threshold","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bc04f980-3957-4e35-ab81-8ec2ffe87215","note":">= 50% of tumour cells with strong (3+) staining"},{"label":"MET amplification (gene copy number)","url":"https://clinicaltrials.gov/study/NCT03778229","note":"SAVANNAH trial (NCT03778229): MET overexpression and/or amplification defined by IHC 90 percent 3+ or FISH 10 or more copies"},{"label":"Human Protein Atlas MET tissue","url":"https://www.proteinatlas.org/ENSG00000105976-MET/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas MET pathology","url":"https://www.proteinatlas.org/ENSG00000105976-MET/pathology","note":"patients per staining level per cancer type (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000105976 associations","url":"https://platform.opentargets.org/target/ENSG00000105976/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:7029","ensembl":"ENSG00000105976","uniprot":"P08581","entrez":"4233","firstDescribed":1985,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Dean et al, Nature, 1985, \"The human met oncogene is related to the tyrosine kinase oncogenes\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/4069211/","biology":"HGF receptor; drives invasion and survival.","whereFound":["NSCLC","Gastric","Papillary RCC","HCC","Non-small-cell lung cancer: splice-site or juxtamembrane alteration deleting exon 14 2-4%","Non-small-cell lung cancer: high-level focal amplification 2-3%"],"targetClass":"kinase","prevalence":[{"cancerId":"nsclc","pct":"3-4","measure":"Exon 14 skipping","source":"https://www.cbioportal.org/study/summary?id=luad_tcga_pan_can_atlas_2018","note":"Amplification in 5-20% post-EGFR TKI; c-MET overexpression ~25% of non-squamous"},{"cancerId":"gastric","pct":"2-5","measure":"Amplification","source":"https://www.cbioportal.org/study/summary?id=stad_tcga_pan_can_atlas_2018"},{"cancerId":"rcc","pct":"10-15","measure":"Papillary RCC type 1 alterations","source":"https://www.cbioportal.org/study/summary?id=kirp_tcga_pan_can_atlas_2018"},{"cancerId":"nsclc","pct":"2-4","measure":"Splice-site or juxtamembrane alteration deleting exon 14","source":"https://www.cbioportal.org/study/summary?id=nsclc_ctdx_msk_2022","note":"cBioPortal, samples with a splice-site or juxtamembrane exon 14 alteration: 96 of 2,621, 3.7%, in nsclc_ctdx_msk_2022; 66 of 2,653, 2.5%, in luad_mskcc_2023_met_organotropism; 27 of 915, 3.0%, in lung_msk_2017; 9 of 566, 1.6%, in luad_tcga_pan_can_atlas_2018; 5 of 232, 2.2%, in lung_nci_2022. Independent counts: 28 of 933 non-squamous lung cancers, 3.0% (Awad 2016); exon 14 skipping was read directly in the messenger RNA of 4% of the 230 TCGA adenocarcinomas (Cancer Genome Atlas Research Network 2014); and the alterations are diverse across tumour types rather than a single hotspot (Frampton 2015)."},{"cancerId":"nsclc","pct":"2-3","measure":"High-level focal amplification","source":"https://www.cbioportal.org/study/summary?id=luad_mskcc_2023_met_organotropism","note":"cBioPortal high-level amplification: 79 of 2,422, 3.3%, in luad_mskcc_2023_met_organotropism; 25 of 915, 2.7%, in lung_msk_2017; 42 of 2,621, 1.6%, in nsclc_ctdx_msk_2022; 11 of 511, 2.2%, in luad_tcga_pan_can_atlas_2018; 8 of 230, 3.5%, in luad_tcga_pub. As a primary driver it is rarer still: MET amplification was the driver in 5 of 733 fully genotyped adenocarcinomas, under 1% (Kris 2014)."}]},"route":"/targets/met/","neighbours":{"biomarker":[{"id":"met-overexpression","kind":"biomarker","name":"c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells)","route":"/biomarkers/met-overexpression/"},{"id":"met-amplification-readout","kind":"biomarker","name":"MET amplification (gene copy number)","route":"/biomarkers/met-amplification-readout/"},{"id":"met-ex14","kind":"biomarker","name":"MET exon 14 skipping mutation","route":"/biomarkers/met-ex14/"}],"cancer":[{"id":"lung-adenocarcinoma","kind":"cancer","name":"Adenocarcinoma of the lung","route":"/cancers/lung-adenocarcinoma/"},{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"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":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"papillary-rcc","kind":"cancer","name":"Papillary renal cell carcinoma","route":"/cancers/papillary-rcc/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"},{"id":"ros1-positive-nsclc","kind":"cancer","name":"ROS1-positive non-small-cell lung cancer","route":"/cancers/ros1-positive-nsclc/"},{"id":"salivary-gland","kind":"cancer","name":"Salivary gland cancers","route":"/cancers/salivary-gland/"},{"id":"pulmonary-sarcomatoid-carcinoma","kind":"cancer","name":"Sarcomatoid carcinoma of the lung","route":"/cancers/pulmonary-sarcomatoid-carcinoma/"}],"drug":[{"id":"al2846","kind":"drug","name":"AL2846","route":"/drugs/al2846/"},{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"bezuclastinib","kind":"drug","name":"Bezuclastinib","route":"/drugs/bezuclastinib/"},{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","route":"/drugs/cabozantinib/"},{"id":"capmatinib","kind":"drug","name":"Capmatinib","route":"/drugs/capmatinib/"},{"id":"capmatinib-tepotinib","kind":"drug","name":"Capmatinib & tepotinib","route":"/drugs/capmatinib-tepotinib/"},{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"glumetinib","kind":"drug","name":"Glumetinib","route":"/drugs/glumetinib/"},{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 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samrotecan","route":"/drugs/tilatamig-samrotecan/"},{"id":"tqb2922","kind":"drug","name":"TQB2922","route":"/drugs/tqb2922/"},{"id":"tqb6411","kind":"drug","name":"TQB6411","route":"/drugs/tqb6411/"},{"id":"vebreltinib","kind":"drug","name":"Vebreltinib","route":"/drugs/vebreltinib/"},{"id":"zanzalintinib","kind":"drug","name":"Zanzalintinib","route":"/drugs/zanzalintinib/"}],"company":[{"id":"apollomics","kind":"company","name":"Apollomics","route":"/companies/apollomics/"},{"id":"imagene-ai","kind":"company","name":"Imagene AI","route":"/companies/imagene-ai/"},{"id":"lucence","kind":"company","name":"Lucence","route":"/companies/lucence/"},{"id":"mythic-therapeutics","kind":"company","name":"Mythic Therapeutics","route":"/companies/mythic-therapeutics/"},{"id":"pathos-ai","kind":"company","name":"Pathos AI","route":"/companies/pathos-ai/"}],"pathway":[{"id":"gastric-cancer-signalling","kind":"pathway","name":"Gastric cancer (KEGG map)","route":"/pathways/gastric-cancer-signalling/"},{"id":"hepatocellular-carcinoma-signalling","kind":"pathway","name":"Hepatocellular carcinoma (KEGG map)","route":"/pathways/hepatocellular-carcinoma-signalling/"},{"id":"invasion-ecm-degradation","kind":"pathway","name":"Invasion: proteases, adhesion & the invasive front","route":"/pathways/invasion-ecm-degradation/"},{"id":"nsclc-signalling","kind":"pathway","name":"Non-small cell lung cancer (KEGG map)","route":"/pathways/nsclc-signalling/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"},{"id":"rtk-activation","kind":"pathway","name":"Receptor tyrosine kinase activation","route":"/pathways/rtk-activation/"},{"id":"renal-cell-carcinoma-signalling","kind":"pathway","name":"Renal cell carcinoma (KEGG 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turns, without stopping the one that works","route":"/ideas/idea-bio1-molecular-progression-add-on/"},{"id":"idea-bio1-upfront-bypass-combination","kind":"idea","name":"Add the second drug on day one when the escape route is predictable","route":"/ideas/idea-bio1-upfront-bypass-combination/"},{"id":"idea-bio1-stromal-resistance-blockade","kind":"idea","name":"Block the survival signals the tumour's neighbours provide","route":"/ideas/idea-bio1-stromal-resistance-blockade/"}],"institution":[{"id":"candiolo","kind":"institution","name":"Istituto di Candiolo IRCCS (FPO)","route":"/institutions/candiolo/"},{"id":"nngm","kind":"institution","name":"nationales Netzwerk Genomische Medizin Lungenkrebs","route":"/institutions/nngm/"},{"id":"shanghai-chest-hospital","kind":"institution","name":"Shanghai Chest Hospital","route":"/institutions/shanghai-chest-hospital/"}]}}