Although an activating BRAF V600E mutation will predict response to BRAF inhibitors in melanoma,1 it may not do so in colorectal cancers because of epidermal growth factor receptor (EGFR) feedback activation with requirement of additional EGFR targeting.5,6 Moreover, non-V600 BRAF mutations might not be responsive to BRAF inhibition at all.7 Thus, one-mutation–one-drug approaches may be ineffective, especially in heavily pretreated patients with cancer. This evidence concerns the gene EGFR and melanoma.