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BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy.
BRAF V600E/K mutations occur in ~50% of melanoma, ~10% of colorectal, ~2% of NSCLC, most papillary thyroid cancers, and hairy-cell leukaemia. BRAF+MEK inhibitor doublets (dabrafenib/trametinib, encorafenib/binimetinib) are standard; encorafenib+cetuximab (+chemotherapy, BREAKWATER) is first-line in BRAF V600E colorectal cancer since 2025-2026. Tumour-agnostic approval of dabrafenib/trametinib exists.
In plain words · BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy.
BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy.
Serine/threonine kinase in the MAPK cascade; class I (V600) mutants are monomer-active and inhibitor-sensitive, class II/III are not.
13 products aim at BRAF: cell therapies, 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-specific alteration: 3 of 3 label readouts filed under it measure a sequence variant (BRAF class II and class III mutations (non-V600), BRAF fusion or rearrangement, BRAF V600E (and V600K)) absent from normal cells. HPA BRAF: RNA low tissue specificity; high antibody staining in 29 normal tissues; highest cancer staining thyroid cancer (4 of 4 high). Distribution: 6 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Skin cancer (all types), Colorectal cancer, Thyroid cancer, Lung cancer (all types), Biliary tract cancer (all types), Brain and spinal cord tumours (all types)); approvals of single-target medicines aimed at it also list Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), not counted; Open Targets associates it with 21 specific cancer types at or above 0.5 (melanoma, colorectal cancer, lung cancer, non-small cell lung carcinoma, lung adenocarcinoma, hepatocellular carcinoma and more). Tissue-agnostic: Dabrafenib US 2014: "With trametinib: BRAF V600E/K metastatic melanoma; later adjuvant melanoma, BRAF V600E NSCLC, anaplastic thyroid cancer,"; Dabrafenib + trametinib US 2022: "BRAF V600E solid tumours, tumour-agnostic (age ≥6)". (Rule 3 of scripts/fetch-target-specificity.ts.)
Sources: BRAF class II and class III mutations (non-V600); BRAF fusion or rearrangement label threshold; BRAF V600E (and V600K) label threshold; Human Protein Atlas BRAF tissue; Open Targets ENSG00000157764 associations
First described 1988. Earliest sequence paper UniProt cites for the protein: Ikawa et al, Mol. Cell. Biol, 1988, "B-raf, a new member of the raf family, is activated by DNA rearrangement". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Cell lines and mouse models for this target →
Serine/threonine kinase in the MAPK cascade; class I (V600) mutants are monomer-active and inhibitor-sensitive, class II/III are not.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Bone marrow, Epididymis, Esophagus, Oral mucosa, Ovary, Salivary gland, Seminal vesicle.
Medium only: pancreatic cancer.
HPA BRAF tissue · HPA BRAF 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 |
|---|---|---|---|---|
| Thyroid cancer | 40-60% | Papillary V600E | Near-universal in some PTC variants | cBioPortal (TCGA) |
| Melanoma | 45-50% | V600 mutation | cBioPortal (TCGA) | |
| Colorectal cancer | 6-18% | V600E mutation | cBioPortal: 575 of 7,237, 7.9%, in crc_msk_2026 (575 of 859 BRAF mutation records); 85 of 1,134, 7.5%, in crc_msk_2017; 88 of 1,516, 5.8%, in crc_eo_2020; 48 of 534, 9.0%, in coadread_tcga_pan_can_atlas_2018; 20 of 224, 8.9%, in coadread_tcga_pub; 111 of 619, 17.9%, in coadread_dfci_2016 (a prospective population cohort, so it captures the older, right-sided, sporadic MSI cases that trial cohorts lose); 23 of 1,015, 2.3%, in crc_sysucc_2022. BRAF mutation was found in 250 of 3,063, 8.2%, of first-line metastatic patients pooled from CAIRO, CAIRO2, COIN and FOCUS (Venderbosch 2014). | cBioPortal (TCGA) |
| Colorectal cancer | 8-12% | V600E mutation | cBioPortal (TCGA) | |
| Non-small-cell lung cancer | 3-4% | Class II and class III mutations (G469X, G466X, K601E, D594X) | cBioPortal, mutation records in luad_mskcc_2023_met_organotropism: G469A 15, G466V 8, D594G 5, G469V 4, K601E 4, D594N 3, against 31 V600E, in the 132 of 2,653 samples with any BRAF mutation (5.0%); in nsclc_ctdx_msk_2022, 60 non-V600 records against 19 V600E in the 79 of 2,621 mutated samples (3.0%); in luad_tcga_pan_can_atlas_2018, 35 non-V600 records against 9 V600E. | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 2-4% | V600E and non-V600 | cBioPortal (TCGA) | |
| Colorectal cancer | 2-4% | Class II and class III mutations (D594, G466, G469, K601, N581) and fusions | 208 of 9,643 sequenced metastatic colorectal cancers, 2.2%, and 22% of all BRAF mutations found (Jones 2017). cBioPortal, mutation records in crc_msk_2026: D594G 46, G469A 9, D594N 9, G466E 6, G469R 6, G469V 5, K601E 4, N581S 4, G466V 3, against 575 V600E; BRAF fusions appear as structural variants in 24 of 7,237 samples (TRIM24-BRAF 9, MKRN1-BRAF 4). | doi.org |
| Gallbladder cancer | 3% | Mutation | Mutation in 7 of 244 samples, 2.9%, in cBioPortal gbc_mskcc_2022 and 5 of 103, 4.9%, in gbc_msk_2018; none of 32 exomes in gbc_shanghai_2014. | cBioPortal (TCGA) |
| Pancreatic ductal adenocarcinoma | 1-3% | Mutation (V600E, in-frame deletion) or fusion | cBioPortal: mutation in 22 of 2,336, 0.9% (N486_P490del 6, V600E 3, V600R 2, T599dup 2), plus 7 fusions (SND1-BRAF 3) in pdac_msk_2024; 3 of 109, all V600E, in paad_utsw_2015, where BRAF mutations were mutually exclusive with KRAS and conferred vemurafenib sensitivity in models (Witkiewicz 2015); 2 of 179 in paad_tcga_pan_can_atlas_2018 and 4 of 395 (V600E 2) in pancreas_msk_2024. 13.0% of 266 KRAS wild-type tumours carried a BRAF mutation and 6.6% a BRAF fusion (Philip 2022). Two of 71 advanced patients carried oncogenic in-frame BRAF deletions, the first clinical evidence that they respond to MAPK pathway inhibition (Aguirre 2018). | cBioPortal (TCGA) |
| Non-small-cell lung cancer | 1-2% | V600E mutation | cBioPortal, V600E records: 31 of 2,653 samples, 1.2%, in luad_mskcc_2023_met_organotropism; 18 of 915, 2.0%, in lung_msk_2017; 19 of 2,621, 0.7%, in nsclc_ctdx_msk_2022; 9 of 566, 1.6%, in luad_tcga_pan_can_atlas_2018; 5 of 230, 2.2%, in luad_tcga_pub. Any BRAF mutation is far commoner: 132 of 2,653 (5.0%), 50 of 915 (5.5%) and 41 of 566 (7.2%). BRAF of any kind was the driver in 16 of 733 fully genotyped adenocarcinomas, 2% (Kris 2014). | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Binimetinib is the MEK inhibitor partnered with encorafenib; blocking the next step in the same relay stops the tumour rerouting around the BRAF block.
Cobimetinib is the MEK partner for vemurafenib, and the first drug approved for histiocytic neoplasms.
Dabrafenib (Tafinlar) is a capsule that switches off the faulty BRAF protein driving some melanomas, lung, thyroid and other cancers. It is almost always paired with trametinib.
Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.
Donafenib is a Chinese redesign of sorafenib that lived longer than the original in a head-to-head liver cancer trial and is approved in China as a first-line option.
Encorafenib is a BRAF inhibitor that, with cetuximab and chemotherapy, became first-line standard for BRAF-mutant colorectal cancer in 2026.
GC101 TIL is an experimental tumour-infiltrating lymphocyte therapy from Shanghai Juncell Therapeutics in phase 2 trials for melanoma, aimed at PD-1 and BRAF.
A blood test that reads a tumour's mutations without a tissue biopsy and is the FDA-approved gateway to several targeted drugs.
The first FDA-approved gene panel that could match one biopsy to several different lung cancer drugs at once.
The first drug ever to extend life in advanced liver cancer (2007), now mostly a comparator arm that newer combinations are measured against.
A family of quick single-gene tests that decide who can have several bowel, lung, breast and bladder cancer drugs.
Tovorafenib is a pill for the most common childhood brain tumour, low-grade glioma driven by BRAF changes, approved in 2024.
Vemurafenib was the first BRAF inhibitor (2011); it shrank melanomas in weeks and proved that a single mutation could be drugged in a solid tumour.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
This is the fusion and immune-marker table for the wild-type minority, the group in which RNA sequencing pays for itself.
Biliary tumours are often diagnosed on tiny biopsies or brushings, so a blood-based panel that detects HER2 amplification and other targets in half of patients is a practical route to testing, with tissue confirmation where the blood is uninformative.
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.
Encorafenib with cetuximab became the standard second-line treatment for BRAF V600E disease, and the platform BREAKWATER later moved into first line with chemotherapy added, doubling survival again.
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 links the molecular route to the practical failure mode: interval cancers after a clear colonoscopy are disproportionately serrated, so detection quality is a molecular problem as much as a technical one.
It is the caution attached to the sidedness rule: a tumour at the hepatic flexure and one at the caecum are both called right-sided and are not the same disease.
Query for this target: (TITLE:"BRAF" OR ABSTRACT:"BRAF") 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 BRAF, not a curated reading list.
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