RAF

Notes

original target text: RAF inhibitor

RAF proteins are a family of enzymes called serine/threonine kinases that act as central relay proteins in the RAS-RAF-MEK-ERK signaling cascade, also known as the MAPK pathway. This pathway transmits growth signals from receptors on the cell surface to the nucleus, where it drives programs of cell division and survival. In many cancers, mutations in RAF itself (most commonly in the BRAF isoform) or in upstream RAS proteins cause this pathway to signal continuously, independent of normal growth cues, driving uncontrolled proliferation. RAF inhibitors are small molecules designed to block the kinase activity of mutant RAF, interrupting this constitutive signal and slowing or halting tumor growth. Because RAF exists as three related isoforms (ARAF, BRAF, and CRAF) that can form dimers with each other, the selectivity profile of a given inhibitor matters: some agents are designed to hit multiple RAF isoforms (pan-RAF inhibitors) to address resistance mechanisms that arise from isoform switching or dimerization, while others are more isoform-selective. This mechanism is broadly relevant to melanoma and other solid tumors bearing RAF or RAS pathway alterations, and pan-RAF strategies are of particular interest for tumors driven by RAS mutations, where single-isoform BRAF inhibitors are typically ineffective.