# MET

Source: https://onco.cc/targets/met/  
OnCo record `met` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Target
- Last checked: 2026-09-04
- Tags: driver; kinase; adc-target
- Symbol: MET
- Class: kinase
- Biology: HGF receptor; drives invasion and survival.
- Where found: 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%

## 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).

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/C-Met
- Wikipedia: https://en.wikipedia.org/wiki/C-Met

## Connected records

- biomarkers: [c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells)](https://onco.cc/biomarkers/met-overexpression/), [MET amplification (gene copy number)](https://onco.cc/biomarkers/met-amplification-readout/), [MET exon 14 skipping mutation](https://onco.cc/biomarkers/met-ex14/)
- cancers: [Adenocarcinoma of the lung](https://onco.cc/cancers/lung-adenocarcinoma/), [EGFR-mutated non-small-cell lung cancer](https://onco.cc/cancers/egfr-mutant-nsclc/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [MET exon 14 and MET-amplified non-small-cell lung cancer](https://onco.cc/cancers/met-altered-nsclc/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Papillary renal cell carcinoma](https://onco.cc/cancers/papillary-rcc/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [ROS1-positive non-small-cell lung cancer](https://onco.cc/cancers/ros1-positive-nsclc/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Sarcomatoid carcinoma of the lung](https://onco.cc/cancers/pulmonary-sarcomatoid-carcinoma/)
- drugs: [AL2846](https://onco.cc/drugs/al2846/), [Amivantamab](https://onco.cc/drugs/amivantamab/), [Bezuclastinib](https://onco.cc/drugs/bezuclastinib/), [Cabozantinib](https://onco.cc/drugs/cabozantinib/), [Capmatinib](https://onco.cc/drugs/capmatinib/), [Capmatinib & tepotinib](https://onco.cc/drugs/capmatinib-tepotinib/), [Crizotinib](https://onco.cc/drugs/crizotinib/), [Glumetinib](https://onco.cc/drugs/glumetinib/), [Guardant360 CDx](https://onco.cc/drugs/guardant360-cdx/), [HDM2017](https://onco.cc/drugs/hdm2017/), [HS-20117](https://onco.cc/drugs/hs-20117/), [JS111](https://onco.cc/drugs/js111/), [LAM561](https://onco.cc/drugs/lam561/), [MCLA-129](https://onco.cc/drugs/mcla-129/), [Savolitinib](https://onco.cc/drugs/savolitinib/), [Telisotuzumab vedotin](https://onco.cc/drugs/telisotuzumab-vedotin/), [Tepotinib](https://onco.cc/drugs/tepotinib/), [Tilatamig samrotecan](https://onco.cc/drugs/tilatamig-samrotecan/), [TQB2922](https://onco.cc/drugs/tqb2922/), [TQB6411](https://onco.cc/drugs/tqb6411/), [Vebreltinib](https://onco.cc/drugs/vebreltinib/), [Zanzalintinib](https://onco.cc/drugs/zanzalintinib/)
- companies: [Apollomics](https://onco.cc/companies/apollomics/), [Imagene AI](https://onco.cc/companies/imagene-ai/), [Lucence](https://onco.cc/companies/lucence/), [Mythic Therapeutics](https://onco.cc/companies/mythic-therapeutics/), [Pathos AI](https://onco.cc/companies/pathos-ai/)
- pathways: [Gastric cancer (KEGG map)](https://onco.cc/pathways/gastric-cancer-signalling/), [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [Invasion: proteases, adhesion & the invasive front](https://onco.cc/pathways/invasion-ecm-degradation/), [Non-small cell lung cancer (KEGG map)](https://onco.cc/pathways/nsclc-signalling/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Receptor tyrosine kinase activation](https://onco.cc/pathways/rtk-activation/), [Renal cell carcinoma (KEGG map)](https://onco.cc/pathways/renal-cell-carcinoma-signalling/), [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/)
- terms: [Amplification](https://onco.cc/terms/amplification/), [Growth factor](https://onco.cc/terms/growth-factor/), [MET amplification (bypass resistance)](https://onco.cc/terms/met-amplification/), [MET exon 14 skipping mutation](https://onco.cc/terms/met-exon-14-skipping/)
- trials: [A First-in-Human Study of CKD-703 in Advanced Solid Tumors and Non-Small Cell Lung Cancer](https://onco.cc/trials/nct07439094/), [COMET-1](https://onco.cc/trials/comet-1/), [FIH Trial of VERT-002 in Patients With Locally Advanced or Metastatic Solid Tumors With MET Alterations](https://onco.cc/trials/nct06669117/), [GEOMETRY mono-1](https://onco.cc/trials/geometry-mono-1/), [LUMINOSITY](https://onco.cc/trials/luminosity/), [MARIPOSA](https://onco.cc/trials/mariposa/), [TeliMET NSCLC-01](https://onco.cc/trials/telimet-nsclc-01/), [VISION (tepotinib)](https://onco.cc/trials/nct02864992/)
- key papers: [Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers](https://onco.cc/key-papers/paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013/), [Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer](https://onco.cc/key-papers/paper-kwak-crizotinib-alk-nsclc-nejm-2010/), [Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib](https://onco.cc/key-papers/paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018/), [Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer](https://onco.cc/key-papers/paper-wolf-geometry-mono-1-capmatinib-nejm-2020/), [Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-aggarwal-plasma-genotyping-personalised-therapy-jama-oncol-2019/), [Comprehensive molecular profiling of lung adenocarcinoma](https://onco.cc/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/), [Genomic and evolutionary classification of lung cancer in never smokers](https://onco.cc/key-papers/paper-zhang-lung-cancer-never-smokers-nat-genet-2021/), [Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors](https://onco.cc/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/), [Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases](https://onco.cc/key-papers/paper-lemmon-schlessinger-rtk-signalling-cell-2010/), [MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer](https://onco.cc/key-papers/paper-mariposa-nejm-2024/), [MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling](https://onco.cc/key-papers/paper-engelman-met-amplification-gefitinib-resistance-science-2007/), [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](https://onco.cc/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/), [MET exon 14 splicing alterations across tumour types and their sensitivity to MET inhibitors](https://onco.cc/key-papers/paper-frampton-met-exon-14-cancer-discov-2015/), [Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma](https://onco.cc/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/), [NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer](https://onco.cc/key-papers/paper-leighl-nile-cfdna-tissue-genotyping-ccr-2019/), [Prospective comprehensive molecular characterization of lung adenocarcinomas for efficient patient matching to approved and emerging therapies](https://onco.cc/key-papers/paper-jordan-prospective-lung-adenocarcinoma-msk-cancer-discov-2017/), [TRACERx first 100: tracking how lung cancers evolve, and how chromosomal chaos predicts relapse](https://onco.cc/key-papers/paper-tracerx-100-nejm-2017/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/), [Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs](https://onco.cc/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/)
- pairings: [Amivantamab + lazertinib (first-line EGFR NSCLC)](https://onco.cc/pairings/amivantamab-plus-lazertinib/)
- technologies: [Antibody-drug conjugate (ADC)](https://onco.cc/technologies/adc/), [Bispecific ADC](https://onco.cc/technologies/bispecific-adc/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [RON receptor (MST1R)](https://onco.cc/targets/ron/)
- people: [Byoung Chul Cho](https://onco.cc/people/cho-byoung-chul/), [Dae Ho Lee](https://onco.cc/people/lee-dae-ho/), [Jürgen Wolf](https://onco.cc/people/juergen-wolf/), [Koichi Goto](https://onco.cc/people/goto-koichi/)
- ideas: [Add a drug when the blood test turns, without stopping the one that works](https://onco.cc/ideas/idea-bio1-molecular-progression-add-on/), [Add the second drug on day one when the escape route is predictable](https://onco.cc/ideas/idea-bio1-upfront-bypass-combination/), [Block the survival signals the tumour's neighbours provide](https://onco.cc/ideas/idea-bio1-stromal-resistance-blockade/)
- institutions: [Istituto di Candiolo IRCCS (FPO)](https://onco.cc/institutions/candiolo/), [nationales Netzwerk Genomische Medizin Lungenkrebs](https://onco.cc/institutions/nngm/), [Shanghai Chest Hospital](https://onco.cc/institutions/shanghai-chest-hospital/)

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JSON: https://onco.cc/api/v1/entities/met.json