RAF kinases

Class

RAF-kinase inhibitor (small molecule, oral, new molecular entity); INN claturafenib — class inferred from the WHO INN stem '-rafenib' (the established stem for RAF-kinase inhibitors, e.g. dabrafenib, encorafenib) combined with Pfizer's own pipeline listing confirming it as a small-molecule oncology NME tested in BRAF V600-mutant tumors alongside binimetinib (MEK inhibitor) and cetuximab (anti-EGFR)

Pathway

RAS-RAF-MEK-ERK signaling

Notes

original target text: RAF kinases (BRAF/CRAF; specific isoform selectivity not stated in the sources checked)

RAF kinases are enzymes that sit within the RAS-RAF-MEK-ERK signaling pathway (also called the MAPK pathway), a chain of molecular signals that instructs cells when to grow and divide. In healthy cells, this pathway is switched on and off in a controlled way. In many cancers, mutations in the BRAF gene—most commonly the V600E mutation—lock the pathway in an active state, driving continuous, unregulated growth signals. RAF-kinase inhibitors are small molecules designed to block this abnormal activity, most directly in tumors carrying BRAF V600 mutations, such as certain melanomas and colorectal cancers.

Because tumor cells often find ways to reactivate the same pathway despite RAF blockade, RAF inhibitors are frequently studied together with other agents that interrupt the pathway at different points—such as MEK inhibitors, which act downstream of RAF, or antibodies against EGFR, a receptor that can restart pathway signaling upstream, particularly in colorectal cancer. Combining agents in this way aims for more durable suppression of the pathway than blocking RAF alone.

This mechanism is broadly relevant wherever BRAF-mutant signaling drives tumor growth, and understanding RAF's role in this pathway helps explain why combination strategies, rather than single-agent RAF blockade, have become a common therapeutic approach in these cancers.