Effective MAPK Inhibition is critical for therapeutic responses in colorectal cancer with BRAF mutations.

RAF inhibitor monotherapy is ineffective in BRAF-mutant colorectal cancer (CRC) but RAF inhibitor combinations have demonstrated improved efficacy, likely through superior suppression of MAPK signaling. The first identified mechanisms of acquired resistance to these combinations all promote MAPK reactivation, underscoring the MAPK pathway as a critical target in BRAF-mutant CRC.