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MEK is the relay in the growth-signal chain that sits just below RAS and RAF. Blocking it starves BRAF- and RAS-driven tumours of their go signal. This dossier gathers the 6 products (4 approved), 31 trials, 7 pathways and 0 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.
Allosteric (non-ATP-competitive) inhibitors lock MEK in an inactive conformation. Toxicities reflect on-target ERK inhibition in normal tissue: rash, diarrhoea, retinal changes (central serous retinopathy), and reduced ejection fraction.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Langerhans cell histiocytosis | 27.5% | Somatic MAP2K1 mutation, 11 of 40 cases, mutually exclusive with BRAF V600E | Found in half of BRAF wild-type cases; the basis for MEK inhibitor use in histiocytosis | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved | Phase 3 | Phase 2 |
|---|---|---|---|
| Small molecule 5 | - | ||
| Cell therapy 1 | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate the Efficacy and Safety of Dabrafenib Plus Trametinib in Previously Treated Patients With Locally Advanced or Metastatic, Radio-active Iodine Refractory BRAFV600E Mutation-positive Differentiated Thyroid Cancer (DTC) | - | ||
BEACON CRC NCT02928224 | 3 | Positive | BRAF V600E-mutant metastatic colorectal cancer after one or two prior lines: encorafenib plus cetuximab with or without binimetinib, versus irinotecan-based chemotherapy plus cetuximab | Median overall survival 9.3 months (encorafenib-cetuximab, with or without binimetinib) vs 5.9 months (chemotherapy plus cetuximab); response rate 20% (doublet) vs 2%. | |
IMblaze370 NCT02788279 | 3 | Negative | Previously treated metastatic colorectal adenocarcinoma, mostly microsatellite-stable: atezolizumab with cobimetinib, or atezolizumab alone, against regorafenib | Median overall survival 8.87 months with atezolizumab and cobimetinib against 8.51 months with regorafenib (hazard ratio 1.00). | |
| 3 | Active | A Phase III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, in Patients Receiving Second Line Treatment for KRAS Mutation-Positive Locally Advanced or Metastatic Non Small Cell Lung Cancer (Stage IIIB - IV) (SELECT 1) | - | ||
coBRIM NCT01689519 | 3 | Positive | Untreated unresectable or metastatic BRAF V600-mutant melanoma: vemurafenib plus cobimetinib versus vemurafenib plus placebo | Median progression-free survival 12.3 vs 7.2 months (HR 0.58); median overall survival 22.3 vs 17.4 months (HR 0.70). | |
COMBI-d NCT01584648 | 3 | Positive | Untreated unresectable or metastatic BRAF V600E or V600K melanoma: dabrafenib plus trametinib versus dabrafenib plus placebo | Median progression-free survival 11.0 vs 8.8 months; median overall survival 25.1 vs 18.7 months (HR 0.71); pooled COMBI-d/v 5-year overall survival 34%. | |
| 3 | Recruiting | A Phase 3 Randomized, Open-Label Study of Atebimetinib in Combination With the Modified Gemcitabine and Nab-Paclitaxel Regimen Versus the Standard Gemcitabine and Nab-Paclitaxel Regimen for the Treatment of Patients With Metastatic Pancreatic Ductal Pancreatic Adenocarcinoma Cancer (MAPKeeper 301) | - | ||
| 3 | Recruiting | Efficacy and Safety of Tunlametinib Capsules Versus Combination Chemotherapy of Investigator's Choice in Advanced NRAS-mutant Melanoma Patients Who Had Previously Received Immunotherapy | - | ||
| 3 | Recruiting | A Multicenter, Randomized, Open-label, Phase 3 Study to Evaluate the Efficacy and Safety of Tunlametinib Plus Vemurafenib in Patients With BRAF V600E-mutant Metastatic Colorectal Cancer | - | ||
| 3 | Completed | Molecular Profiling of Advanced Soft-tissue Sarcomas. A Phase III Study | - | ||
| 2/3 | Recruiting | DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage/Young Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. | - | ||
NCI-MATCH (EAY131) NCT02465060 | platform | Active | Advanced solid tumours, lymphomas and myeloma that have progressed on standard treatment: central tumour sequencing assigns patients to one of nearly 40 single-agent or doublet targeted-therapy arms by molecular alteration regardless of cancer type | 5,954 patients enrolled; 17.8 percent assigned to an arm. Dabrafenib plus trametinib in BRAF V600 tumours (38 percent response) and nivolumab in dMMR non-colorectal tumours (36 percent) were positive; most single-agent arms were not. | |
National Lung Matrix Trial NCT02664935 | 2 | Completed | Advanced non-small-cell lung cancer after first-line treatment, screened nationally through the Cancer Research UK Stratified Medicine Programme: 22 biomarker-defined cohorts of eight targeted drugs | Most of the 22 biomarker-drug cohorts did not meet their pre-set efficacy thresholds; the trial demonstrated national molecular screening and the limits of single-agent matching. | |
| 2 | Positive | BRAF V600E-mutated rare cancers in nine histology cohorts, including previously treated unresectable, metastatic or recurrent biliary tract cancer (n=43): dabrafenib 150 mg twice daily plus trametinib 2 mg daily, single arm | Biliary cohort ORR 51% (22/43, investigator) and 47% (independent review); grade 3 or worse GGT rise 12%. | ||
CheckMate 142 NCT02060188 | 2 | Positive | Recurrent or metastatic colorectal cancer, MSI-high and non-MSI-high cohorts: nivolumab alone or with ipilimumab, and later cohorts adding cobimetinib, daratumumab or relatlimab | dMMR nivolumab plus ipilimumab cohort: objective response 55 percent, twelve-month overall survival 85 percent. MSS cohort with cobimetinib: objective response 3 percent. | |
| 2 | Positive | Previously untreated metastatic BRAF V600E-mutant non-small-cell lung cancer: dabrafenib 150 mg twice daily with trametinib 2 mg daily, single arm, with investigator-assessed objective response as the primary endpoint | Confirmed objective response 64 percent (23 of 36), with 6 percent complete responses; grade 3 or worse adverse events in 69 percent. | ||
A Phase II Study of GC101 in NSCLC NCT07560111 | 2 | Recruiting | An Open-Label, Phase II Study to Evaluate the Safety and Efficacy Using Autologous Tumor Infiltrating Lymphocytes Injection (GC101 TIL) in Patients With Non-Small Cell Lung Cancer | - | |
| 2 | Active | A Randomized Phase II Trial of MEK Inhibitor Selumetinib (AZD6244) Combined Continuously or Sequentially With Cisplatin/Gemcitabine (CIS/GEM) Versus CIS/GEM Alone in Patients With Advanced Biliary Cancer | - | ||
A Study of GC101 TIL in Advanced Melanoma NCT06703398 | 2 | Recruiting | A Multicenter, Randomized, Controlled,Open Label, Phase II Trial of Autologous Tumor Infiltrating Lymphocytes (GC101 TIL) in Subjects With Advanced Melanoma | - | |
Mirdametinib in Histiocytic Disorders NCT06153173 | 2 | Recruiting | A Phase II Trial of the MEK Inhibitor Mirdametinib in Histiocytic Disorders | - | |
| 2 | Recruiting | A Pilot Study of Mirdametinib in Patients With Advanced Melanoma With an NF1 Mutation | - | ||
Pan Tumor Rollover Study NCT03899155 | 2 | Recruiting | Pan-Tumor Study for Long-term Treatment of Cancer Patients Who Have Participated in BMS Sponsored Trials Investigating Nivolumab and Other Cancer Therapies | - | |
| 2 | Active | A Randomized, Open-label, Multi-arm, Two-part, Phase II Study to Assess Efficacy and Safety of Multiple LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic BRAFV600 or NRAS Mutant Melanoma | - | ||
| 2 | Recruiting | A Phase 2 Pilot Study of Mirdametinib in Relapsed Refractory Chronic Lymphocytic Leukemia | - | ||
| 1/2 | Recruiting | An Exploratory Phase 1b/2a Multicenter, Open-Label, Novel-Novel Combination Study to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of CC-92480 (BMS-986348) in Novel Therapeutic Combinations in Participants With Relapsed or Refractory Multiple Myeloma | - | ||
| 1/2 | Recruiting | Phase 1b/2a Study of GNS561 in Combination With Trametinib in Advanced KRAS Mutated Cholangiocarcinoma | - | ||
| 1/2 | Active | KontRASt-03: A Phase Ib/II, Multicenter, Open-label Platform Study of JDQ443 With Select Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation | - | ||
| 1/2 | Recruiting | KontRASt-R: An Open-label, Multi-center, Rollover Study for Participants Who Have Been Previously Enrolled Into a Novartis-sponsored Opnurasib (JDQ443) Study and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments | - | ||
| 1/2 | Recruiting | Phase I/II Study of the MEK Inhibitor Selumetinib Plus DS-8201a (Trastuzumab Deruxtecan) in KRAS-Mutant, HER2-Expressing Pancreatic Ductal Adenocarcinoma | - | ||
| 1/2 | Planned | Trametinib Plus Anlotinib Combined With Tislelizumab in KRAS-mutant Advanced Non-small Cell Lung Cancer Patients: a Multi-center, Open-label, Phase 1/2 Study | - |
No recorded escape route names this target.
KEGG's AML map shows the two hits that turn a normal blood stem cell into a leukaemia: a growth signal jammed on (FLT3, KIT or RAS) plus a broken maturation switch (fusion proteins such as PML-RARA or AML1-ETO, or mutated CEBPA and RUNX1). Drugs now exist for both halves.
Which nodes have drugs →KEGG's bladder cancer map shows two routes: low-grade papillary tumours driven by FGFR3 or HRAS activating the MAPK relay, and high-grade invasive tumours that lose TP53 and RB1. Erdafitinib targets the first route; antibody-drug conjugates and PD-1 antibodies now anchor treatment of the second.
Which nodes have drugs →KEGG's breast cancer map lays out the three clinical subtypes as signalling routes: oestrogen receptor driving cyclin D and CDK4/6 in hormone-receptor-positive disease, HER2 driving PI3K/AKT and MAPK in HER2-positive disease, and EGFR, Notch, Wnt and BRCA defects in triple-negative disease. Each route has its own drug class.
Which nodes have drugs →KEGG's CML map is built around one fusion protein, BCR-ABL1, a kinase that never switches off and drives RAS, PI3K and STAT5 signalling. Because a single enzyme causes the disease, a single class of pill (imatinib and its successors) controls it in most patients.
Which nodes have drugs →KEGG's melanoma map shows BRAF or NRAS mutations driving the MAPK growth relay, PTEN loss driving PI3K/AKT, and loss of the CDKN2A brakes (p16 and p14ARF) on CDK4/6 and p53. BRAF plus MEK inhibitors and immune checkpoint antibodies have transformed treatment.
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 →This KEGG map shows thyroid cancers driven by one relay, the MAPK pathway: RET or NTRK fusions and BRAF mutations in papillary tumours, RAS mutations or PAX8-PPARG fusion in follicular tumours, and TP53 loss marking anaplastic cancer. It matters because RET, NTRK and BRAF alterations each have their own drug, and MAPK blockade can restore iodine uptake.
Which nodes have drugs →No companion diagnostic in the registry measures this target.
No model entry for this target yet; check the cancer entries on the models page.
No open questions recorded for this target yet. Suggest one.
Query for this target: (TITLE:"MEK1/2" OR ABSTRACT:"MEK1/2" OR TITLE:"MAP2K1" OR ABSTRACT:"MAP2K1" OR TITLE:"MAP2K2" OR ABSTRACT:"MAP2K2") 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 MEK1/2, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/mek.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/mek.json. Licence CC BY-NC 4.0.