BRAF V600E/V600K/V600D (also wild-type BRAF/CRAF)

Class

BRAF kinase inhibitor

Pathway

RAS-RAF-MEK-ERK (MAPK) signaling

BRAF is an intracellular signaling enzyme, a kinase, that operates within the RAS-RAF-MEK-ERK pathway (also called the MAPK pathway), a chain of proteins that relays signals from growth-factor receptors on the cell surface to the nucleus, where they direct cell division and survival. In healthy cells, BRAF activity is tightly controlled by upstream RAS proteins. Point mutations at codon 600 of the BRAF gene, most commonly V600E and less often V600K or V600D, lock the kinase into a permanently active state, so the pathway fires continuously regardless of external signals. This drives uncontrolled proliferation in several cancers, most notably melanoma, but also thyroid, colorectal, and other solid tumors carrying these mutations. BRAF kinase inhibitors are small molecules designed to occupy the enzyme's active site and suppress this constitutive signaling, aiming to selectively shut down the mutant, cancer-driving form of BRAF while sparing normal cellular use of the same pathway elsewhere. Because these mutations concentrate signaling dependence onto a single, identifiable molecular defect, they represent a clear example of a genetically defined drug target: tumors bearing a V600 mutation are markedly reliant on continued MAPK output, making pharmacological interruption of BRAF itself a rational therapeutic strategy in this disease context.