A receptor that is either mutated in some lung cancers or amplified as an escape route when other lung cancer drugs fail. This dossier gathers the 6 products (5 approved), 7 trials, 2 pathways and 5 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Biology
HGF receptor; drives invasion and survival.
- NSCLC
- Gastric
- Papillary RCC
- HCC
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| 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) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Mutation hotspots and which drugs address them
| Residue | Kind | How common | What it does | Addressed by | Defeats | Source |
|---|---|---|---|---|---|---|
| Exon 14 skipping (splice sites around D1010, Y1003) 1003 to 1010 | Activating | About 3% of NSCLC | Loss of the CBL-binding juxtamembrane exon stabilises the receptor. Capmatinib and tepotinib are approved; crizotinib is active. | — | Frampton et al., Cancer Discov 2015 | |
| D1228N/H and Y1230C/H 1228 | Resistance | not sourced | Activation-loop mutations after type I MET TKIs (capmatinib, tepotinib, crizotinib); type II inhibitors (cabozantinib) retain activity preclinically. Antibody-based agents are genotype-independent. | Frampton et al., Cancer Discov 2015 |
Frequencies are quoted from the source on each row; a blank means no figure was sourced, not that it is rare. Domain boundaries are approximate. Sources for the map: Cancer Hotspots (MSK) · COSMIC: MET.
Products by modality and phase
Browse products →| Modality | Approved | Phase 2 |
|---|---|---|
| Small molecule 2 | — | |
| ADC 1 | — | |
| Bispecific ADC 1 | — | |
| Bispecific antibody 1 | — | |
| Small-molecule ALK/ROS1/MET TKI 1 | — |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| CABINET (Alliance A021602) NCT03375320 | 3 | Positive | Previously treated advanced pancreatic (n=95) and extra-pancreatic (n=203) NETs: cabozantinib vs placebo | PFS HR 0.23 (pNET), 0.38 (epNET). | |
| CONTACT-03 NCT04338269 | 3 | Negative | Advanced RCC progressing on or after a PD-1/PD-L1 inhibitor: atezolizumab + cabozantinib vs cabozantinib | PFS HR 1.03; OS HR 0.94, negative. | |
| MARIPOSA NCT04487080 | 3 | Positive | First-line EGFR-mutant NSCLC: amivantamab + lazertinib vs osimertinib | PFS HR 0.70; OS HR 0.75. | |
| COSMIC-313 NCT03937219 | 3 | Mixed | Untreated intermediate/poor-risk clear-cell RCC: cabozantinib + nivolumab + ipilimumab vs nivolumab + ipilimumab | PFS HR 0.73; OS HR 1.02 (no benefit). | |
| CheckMate 9ER NCT03141177 | 3 | Positive | Untreated advanced clear-cell RCC: nivolumab + cabozantinib vs sunitinib | PFS HR 0.51; OS HR 0.77 at ~4 years (46.5 vs 36.0 months). | |
| CELESTIAL NCT01908426 | 3 | Positive | HCC after sorafenib (up to two prior lines): cabozantinib vs placebo | OS 10.2 vs 8.0 months, HR 0.76. | |
| TeliMET NSCLC-01 NCT04928846 | 3 | Recruiting | Previously treated c-Met-overexpressing, EGFR-wild-type non-squamous NSCLC: telisotuzumab vedotin vs docetaxel |
Resistance routes that involve this target
Unaddressed routes →Mutation of the cysteine that osimertinib binds covalently; abolishes drug binding while EGFR stays active.
- Fourth-generation allosteric EGFR inhibitors (in trials); amivantamab-based regimens
- ADCs that bypass genotype: Dato-DXd, HER3-DXd, iza-bren
Amplified MET signals to PI3K/MAPK independently of EGFR.
- EGFR×MET bispecific amivantamab; MET TKI + osimertinib combinations
- c-MET-directed and EGFR×c-MET bispecific ADCs
Conversion to small-cell lung cancer (RB1/TP53 co-loss) or squamous histology; EGFR mutation persists but the cell no longer depends on it.
- Re-biopsy at progression; platinum-etoposide for SCLC transformation
Alternative receptors or downstream mutations re-activate MAPK/PI3K.
- Combination with MET or MEK inhibitors (trials); chemotherapy; ADCs
Alternative MAPK activation.
- Combination with MEK/ERK inhibitors; re-biopsy-guided therapy
Pathways where it is a node
Pathway-to-drug matrix →- Receptor tyrosine kinase activationNode: Bypass RTK (MET, HER3) · 5 druggable nodes
Growth-factor receptors are antennas on the cell surface that pair up when a signal lands and switch on the growth relays inside. Cancers mutate, multiply, or fuse these antennas so they broadcast 'grow' with no signal at all. Most targeted drugs, antibodies and ADCs start here.
Which nodes have drugs → - Resistance routes: how a blocked pathway comes backNode: 2 Bypass RTK (MET, HER3) · 6 druggable nodes
When a drug blocks a cancer's engine, the cancer has five ways back: change the part the drug binds, make more of it, take a side road, switch to a different engine altogether, or stop letting the drug in. Knowing which route a tumour took decides the next drug.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| FoundationOne CDx Foundation Medicine (Roche) · FDA CDx 2017 | NGS tissue | Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase | |
| Oncomine Dx Target Test Thermo Fisher Scientific · FDA CDx 2017 | NGS tissue | Per companion claim: BRAF V600E (dabrafenib plus trametinib), ROS1 fusions (crizotinib), EGFR (gefitinib), RET fusions (pralsetinib), MET exon 14 (tepotinib), EGFR exon 20 insertions |
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →- 01
What definition of MET amplification or overexpression should select patients for MET-directed drugs at EGFR-TKI progression?
translationalregulatorWhy unresolved. Copy-number thresholds by FISH, NGS and IHC disagree; MARIPOSA showed amivantamab's benefit without MET selection, while MET TKI combinations depend on it.
What would answer it. Harmonised MET assay validation against outcomes in a randomised trial at osimertinib progression.
Source: MARIPOSA, NEJM 2024
Ideas and companies
Key papers and the live literature
Preprints →- MARIPOSA: amivantamab plus lazertinib versus osimertinib as first treatment for EGFR-mutated lung cancer · New England Journal of Medicine 2024
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.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/met.json. Licence CC BY 4.0.