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A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.
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.
In plain words · A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.
Backbone ribbon from PDB 6WVZ. RCSB PDB 6WVZ. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail.
HGF receptor; drives invasion and survival.
22 products aim at MET: antibody-drug conjugates, bispecific antibodies, small molecules and other agents. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
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.)
Sources: c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells) label threshold; MET amplification (gene copy number); Human Protein Atlas MET tissue; Human Protein Atlas MET pathology; Open Targets ENSG00000105976 associations
First described 1985. Earliest sequence paper UniProt cites for the protein: Dean et al, Nature, 1985, "The human met oncogene is related to the tyrosine kinase oncogenes". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
HGF receptor; drives invasion and survival.
RNA: tissue enhanced (liver 40 nTPM), detected in many normal tissues.
Medium: Adrenal gland, Appendix, Bronchus, Caudate, Cerebellum, Colon, Endometrium, Epididymis.
Medium only: breast cancer, carcinoid, glioma, liver cancer.
HPA MET tissue · HPA MET pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Renal cell carcinoma | 10-15% | Papillary RCC type 1 alterations | cBioPortal (TCGA) | |
| Non-small-cell lung cancer | 3-4% | Exon 14 skipping | Amplification in 5-20% post-EGFR TKI; c-MET overexpression ~25% of non-squamous | cBioPortal (TCGA) |
| Gastric & gastro-oesophageal junction cancer | 2-5% | Amplification | cBioPortal (TCGA) | |
| Non-small-cell lung cancer | 2-4% | Splice-site or juxtamembrane alteration deleting exon 14 | 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). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 2-3% | High-level focal amplification | 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). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
AL2846 is an experimental small-molecule drug from Chia Tai Tianqing Pharmaceutical in phase 3 trials for thyroid cancer, aimed at MET and RET.
A two-armed antibody that blocks EGFR and its escape partner MET, now first-line for EGFR-mutant lung cancer with lazertinib.
Bezuclastinib is an experimental small-molecule drug from Cogent Biosciences in phase 3 trials for gastrointestinal stromal tumour, aimed at KIT and MET.
A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.
Capmatinib is a targeted pill for the small group of lung cancers driven by a MET exon 14 skipping mutation, found by tumour sequencing.
Capmatinib and tepotinib are two pills for the roughly 3% of lung cancers with a MET exon 14 skipping mutation.
Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.
Glumetinib is a Chinese MET inhibitor approved in 2023 for lung cancers with MET exon 14 skipping, one of three such drugs approved in China and now in a phase 3 trial in gastric cancer.
A blood test that reads a tumour's mutations without a tissue biopsy and is the FDA-approved gateway to several targeted drugs.
HDM2017 is an experimental investigational agent whose form is not stated in the registry from Hangzhou Zhongmei Huadong Pharmaceutical in phase 2 trials for colorectal cancer, aimed at MET.
HS-20117 is an experimental bispecific antibody from Hansoh BioMedical R&D in phase 3 trials for non-small-cell lung cancer, aimed at EGFR and MET.
JS111 is an experimental small-molecule drug from Suzhou Junjing BioSciences in phase 2 trials for non-small-cell lung cancer, aimed at EGFR and MET.
LAM561 is an experimental small-molecule drug from Laminar Pharmaceuticals in phase 3 trials for glioma & glioblastoma, aimed at MET.
MCLA-129 is an experimental bispecific antibody from Betta Pharmaceuticals in phase 2 trials for non-small-cell lung cancer, head and neck squamous cell carcinoma and colorectal cancer, aimed at EGFR and MET.
Savolitinib is a Chinese-discovered pill that blocks the MET growth signal, approved in China for lung cancers with a MET exon 14 mutation and being tested worldwide with osimertinib.
Telisotuzumab vedotin (Emrelis) is the first c-MET-directed ADC, approved in 2025 for lung cancer with high c-MET protein.
Tepotinib is a once-daily targeted pill for lung cancers driven by a MET exon 14 skipping mutation, and the MET inhibitor NICE funds in England.
AstraZeneca's EGFR×c-MET bispecific ADC, the most advanced in the most crowded next-generation ADC target pair.
TQB2922 is an experimental bispecific antibody from Chia Tai Tianqing Pharmaceutical Nanjing Shunxin Pharmaceutical in phase 2 trials for colorectal cancer, aimed at EGFR and MET.
TQB6411 is an experimental antibody-drug conjugate from Chia Tai Tianqing Pharmaceutical in phase 2 trials for non-small-cell lung cancer and oesophageal cancer, aimed at EGFR and MET.
Vebreltinib is a Chinese MET inhibitor approved in 2023 for lung cancers with a MET exon 14 skipping mutation, and the first drug tested in a phase 3 trial for glioblastomas carrying a PTPRZ1-MET fusion.
Zanzalintinib is an experimental small-molecule drug from Exelixis in phase 3 trials for neuroendocrine tumours, head and neck squamous cell carcinoma and renal cell carcinoma, aimed at VEGF / VEGFR and MET.
Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
A rare driver with a real drug, and a warning about biomarker thresholds: the same gene, tested the same way, predicts response or does not depending on a copy-number cut-off that has to be measured rather than assumed.
It showed the benefit of plasma testing is not only analytical but logistical: it reaches patients who are too unwell, or whose disease is too inaccessible, for a repeat biopsy.
It is the evidence behind running plasma and tissue together at diagnosis rather than in sequence, and the 80% sensitivity figure is the reason a negative plasma result never ends the work-up.
It changed how resistance is investigated: the first question at progression on osimertinib is whether T790M is still there, because losing it means the tumour is no longer EGFR-driven in the growing compartment and another EGFR inhibitor will not help.
It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.
Query for this target: (TITLE:"MET" OR ABSTRACT:"MET") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about MET, not a curated reading list.
Shares HS-20117, JS111, TQB2922, TQB6411 and the tags driver, kinase.
Shares AL2846, Koichi Goto, Imagene AI, Lucence and the tags driver, kinase.
Shares Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases, Imagene AI, Lucence, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer and the tags driver, kinase.
Shares Koichi Goto, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer, NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer, nationales Netzwerk Genomische Medizin Lungenkrebs and the tags driver, kinase.
Shares Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases, Koichi Goto, Imagene AI, Amplification and the tags driver, adc-target.
Shares Imagene AI, Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer, NILE: clinical utility of comprehensive cell-free DNA analysis to identify genomic biomarkers in patients with newly diagnosed metastatic non-small cell lung cancer, Add the second drug on day one when the escape route is predictable and the tags driver, kinase.
Shares AL2846, Lemmon and Schlessinger 2010: cell signalling by receptor tyrosine kinases, Bezuclastinib, PI3K / AKT / mTOR and the tags driver, kinase.
Shares Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma, Gastric cancer (KEGG map), PI3K / AKT / mTOR, Receptor tyrosine kinase activation and the tags driver, kinase.