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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. This dossier gathers the 22 products (11 approved), 119 trials, 5 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.
HGF receptor; drives invasion and survival.
| 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.
| 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.
| Modality | Approved | Phase 3 | Phase 2 |
|---|---|---|---|
| Small molecule 11 | |||
| Bispecific antibody 4 | |||
| ADC 2 | - | ||
| Bispecific ADC 1 | - | - | |
| not stated 1 | - | - | |
| Small-molecule ALK/ROS1/MET TKI 1 | - | - | |
| Small-molecule selective MET TKI 1 | - | - | |
| Test or device 1 | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
LITESPARK-011 NCT04586231 | 3 | Positive | Advanced clear-cell renal cell carcinoma that has progressed after anti-PD-1 or anti-PD-L1 therapy: belzutifan 120 mg plus lenvatinib 20 mg versus cabozantinib 60 mg, all oral once daily, open label, randomised 1:1 | Final progression-free survival 14.8 vs 10.7 months (hazard ratio 0.70, 95% CI 0.59 to 0.84; one-sided p<0.0001). Interim overall survival 34.9 vs 27.6 months (hazard ratio 0.85, 0.68 to 1.05; one-sided p 0.061), not statistically significant. Data cutoff 9 April 2025. | |
| 3 | Active | A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure | - | ||
| 3 | Active | A Phase 3, Randomized, Open-Label, Controlled Study of Cabozantinib (XL184) in Combination With Atezolizumab vs Second Novel Hormonal Therapy (NHT) in Subjects With Metastatic Castration-Resistant Prostate Cancer | - | ||
| 3 | Active | A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination With Atezolizumab Versus Sorafenib in Subjects With Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy | - | ||
| 3 | Active | A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer | - | ||
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). | |
| 3 | Active | A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Cabozantinib (XL184) in Subjects With Radioiodine-Refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Vascular Endothelial Growth Factor Receptor (VEGFR) -Targeted Therapy | - | ||
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). | |
eXalt3 NCT02767804 | 3 | Positive | Advanced ALK-positive non-small-cell lung cancer with no prior ALK inhibitor: ensartinib versus crizotinib | Median progression-free survival 25.8 vs 12.7 months (hazard ratio 0.51, blinded independent review, intent-to-treat); intracranial response 63.6% vs 21.1% in patients with target brain metastases. | |
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). | |
| 3 | Active | A Phase III, Open Label, Randomised, Controlled, Multi-Centre Study To Assess the Efficacy and Safety of Savolitinib Versus Sunitinib in Patients With MET-Driven, Unresectable and Locally Advanced, Or Metastatic Papillary Renal Cell Carcinoma (PRCC) | - | ||
ALESIA NCT02838420 | 3 | Positive | Untreated ALK-positive non-small-cell lung cancer in Asian patients: alectinib 600 mg twice daily versus crizotinib 250 mg twice daily, with investigator-assessed progression-free survival as the primary endpoint | Investigator-assessed progression-free survival significantly longer with alectinib than crizotinib, consistent with the global ALEX trial. | |
ALTA-1L NCT02737501 | 3 | Positive | Untreated advanced ALK-positive non-small-cell lung cancer: brigatinib versus crizotinib | Median progression-free survival 24.0 vs 11.1 months (hazard ratio 0.48, blinded independent review, final analysis). | |
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. | |
ALEX NCT02075840 | 3 | Positive | Untreated advanced ALK-positive non-small-cell lung cancer: alectinib versus crizotinib | Median progression-free survival 34.8 vs 10.9 months (hazard ratio 0.43); 12-month brain progression 9.4% vs 41.4%; 5-year overall survival 62.5% vs 45.5%. | |
| J-ALEX | 3 | Positive | ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer, chemotherapy-naive or after one regimen: alectinib 300 mg twice daily versus crizotinib 250 mg twice daily, with progression-free survival by an independent review facility as the primary endpoint | Stopped at the second interim analysis for a large progression-free survival advantage of alectinib over crizotinib. | |
COMET-1 NCT01605227 | 3 | Negative | Metastatic castration-resistant prostate cancer progressing after docetaxel and abiraterone or enzalutamide: cabozantinib 60 mg once daily against prednisone 5 mg twice daily, randomised 2:1, with overall survival as the primary endpoint and bone scan response at week 12 as the secondary endpoint | Median overall survival 11.0 against 9.8 months (hazard ratio 0.90, 95 percent confidence interval 0.76 to 1.06, p=0.213): not met. Bone scan response at 12 weeks 42 against 3 percent and radiographic progression-free survival 5.6 against 2.8 months. | |
PROFILE 1014 NCT01154140 | 3 | Positive | Untreated advanced ALK-positive non-squamous non-small-cell lung cancer: crizotinib 250 mg twice daily versus pemetrexed with cisplatin or carboplatin for up to six cycles, with progression-free survival by independent radiological review as the primary endpoint and crossover allowed | Median progression-free survival 10.9 against 7.0 months (hazard ratio 0.45, 95 percent confidence interval 0.35 to 0.60). | |
EXAM NCT00704730 | 3 | Positive | Progressive metastatic medullary thyroid cancer: cabozantinib against placebo | Cabozantinib lengthened progression-free survival compared with placebo in progressive medullary thyroid cancer; approved in November 2012. | |
| 3 | Recruiting | A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors | - | ||
| 3 | Recruiting | A Phase 3, Randomized, Double-blind, Study of Belzutifan + Zanzalintinib Versus Belzutifan + Placebo in Participants With Advanced RCC Who Have Progressed on or After Both PD-1/L1 and VEGF-TKI Therapies in Sequence or in Combination (LITESPARK-034) | - | ||
| 3 | Recruiting | A Phase 3, Randomized, Open-label Study of Belzutifan + Zanzalintinib Versus Cabozantinib in Participants With Advanced RCC Who Experienced Disease Recurrence During or After Prior Adjuvant Anti-PD-1/L1 Therapy (LITESPARK-033) | - | ||
| 3 | Recruiting | An Open, Multi-center, Single-arm Phase IIIb Confirmatory Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Vebreltinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer With MET Exon 14 Mutation | - | ||
| 3 | Recruiting | A Phase 3 Multicenter Open-label Study of Taletrectinib Versus a Standard of Care ROS1-Tyrosine Kinase Inhibitor (Crizotinib) in TKI-Naïve Patients With ROS1-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (TRUST-III) | - | ||
| 3 | Recruiting | A Randomized, Double-Blind, Multicenter Phase III Clinical Trial Evaluating AL2846 Capsule Versus Placebo in Patients With Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma Who Failed Prior VEGFR-Targeted Therapy | - | ||
| 3 | Recruiting | A Randomized, Open-label Phase 3 Study of Amivantamab + FOLFIRI Versus Cetuximab/Bevacizumab + FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Recurrent, Unresectable or Metastatic Colorectal Cancer Who Have Received Prior Chemotherapy | - | ||
| 3 | Recruiting | A Randomized, Open-label Phase 3 Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer | - | ||
| 3 | Recruiting | A Phase 3, Randomized, Open-Label, Multicenter Study of Amivantamab in Addition to Carboplatin and Pembrolizumab, Compared to Standard of Care Platinum and Pembrolizumab and 5-FU, in Participants With Treatment-Naïve Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma | - |
Mutation of the cysteine that osimertinib binds covalently; abolishes drug binding while EGFR stays active.
Amplified MET signals to PI3K/MAPK independently of EGFR.
Conversion to small-cell lung cancer (RB1/TP53 co-loss) or squamous histology; EGFR mutation persists but the cell no longer depends on it.
Alternative receptors or downstream mutations re-activate MAPK/PI3K.
Alternative MAPK activation.
This KEGG map shows how hepatitis viruses, alcohol and aflatoxin leave the liver with mutations in telomerase, TP53, Wnt/beta-catenin, PI3K/AKT/mTOR and the oxidative stress sensor NRF2, which together drive liver cancer. It matters because the map explains why liver cancer is treated mainly with angiogenesis blockers and immunotherapy rather than a single targeted drug.
Which nodes have drugs →KEGG's non-small cell lung cancer map shows a set of alternative on-switches (EGFR mutation, KRAS mutation, EML4-ALK, RET and MET alterations) that all feed the same RAS/ERK, PI3K/AKT and STAT relays, plus loss of the p16 and p53 brakes. Each on-switch now has its own targeted pill, which is why molecular testing comes before treatment.
Which nodes have drugs →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 →KEGG's kidney cancer map shows how losing VHL lets the oxygen sensor HIF pile up and order new blood vessels (VEGF, PDGF), while MET and PI3K drive growth in other subtypes. Anti-VEGF drugs, HIF-2a inhibitors and immunotherapy all act on this circuit.
Which nodes have drugs →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 →| 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 |
No model entry for this target yet; check the cancer entries on the models page.
Why 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 2024Query 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.
The dossier as machine-readable JSON, at /api/v1/dossiers/met.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-NC 4.0.