BRAF
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
BRAF is a signalling kinase mutated in half of melanomas; blocking it with two drugs at once became a template for targeted therapy.
- 2 · What goes wrong in cancer
Serine/threonine kinase in the MAPK cascade; class I (V600) mutants are monomer-active and inhibitor-sensitive, class II/III are not.
- 3 · How drugs use it
7 products aim at BRAF: small molecules. Kinases are switched on by binding ATP inside the cell, so most drugs are small molecules shaped to plug that ATP pocket.
Biology
Serine/threonine kinase in the MAPK cascade; class I (V600) mutants are monomer-active and inhibitor-sensitive, class II/III are not.
- Melanoma
- Colorectal
- Thyroid
- NSCLC
- Glioma (paediatric)
How common it is, by cancer
| 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 | 8-12% | V600E mutation | cBioPortal (TCGA) | |
| Non-small-cell lung cancer | 2-4% | V600E and non-V600 | 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 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.
Encorafenib is a BRAF inhibitor that, with cetuximab and chemotherapy, became first-line standard for BRAF-mutant colorectal cancer in 2026.
The first drug ever to extend life in advanced liver cancer (2007), now mostly a comparator arm that newer combinations are measured against.
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.
There are not thousands of cancer genes, and any one patient's tumour is driven by only a few of them. That makes targeted sequencing panels sensible, but because most drivers are lost tumour suppressors, drugs exist for only a minority, which is why the same group turned to early detection.
Latest papers
topQuery 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.