Although BRAF inhibitor monotherapyis effective in patients with melanoma and BRAF V600Emutations, it has produced low response rates in BRAFV600E-mutated CRCs.60 Evidence from preclinical studies suggest that this lack of response iscaused by feedback reactivation of EGFR and subsequent initiation of downstreamsignaling.61,62 For this reason, combination therapies targetingmultiple points along the MAPK pathway have been investigated inBRAF V600-mutated CRC. The gene discussed is BRAF; the disease is melanoma.