BRAF V600 mutations

Class

BRAF inhibitor (small molecule); studied with binimetinib (MEK inhibitor)

Pathway

RAS-RAF-MEK-ERK pathway blockade

BRAF is an enzyme (a kinase) that relays growth signals through the RAS-RAF-MEK-ERK pathway, a chain of protein activations that normally controls when cells divide in response to external cues. In a subset of cancers, a single point mutation—most commonly at position V600—locks BRAF into a permanently active state, so the pathway fires continuously regardless of upstream signals, driving uncontrolled proliferation. This mutation is found across several tumor types, including melanoma, thyroid cancer, and some colorectal and lung cancers, making V600-mutant BRAF one of the most extensively targeted oncogenic drivers. BRAF inhibitors are small molecules designed to selectively block the mutant, hyperactive form of the enzyme, shutting down this proliferative signal in tumor cells while sparing cells with normal BRAF. Because tumors frequently develop ways to reactivate the same pathway downstream, BRAF inhibitors are often paired with MEK inhibitors, which block the next enzyme in the chain, providing a second point of blockade. This vertical, two-node inhibition strategy is intended to produce a more durable suppression of the pathway than blocking BRAF alone. Newer BRAF inhibitors are also being engineered to avoid triggering unwanted activation of the pathway in cells that carry normal, non-mutated BRAF, a phenomenon associated with earlier-generation agents.