In contrast to dramatic responses obtained in BRAF V600E-mutant melanomas (RR of 48 to 67 %) [13, 56], selective BRAF inhibitors such as vemurafenib have failed in BRAF-mutant CRCs (RR of 5 %) [57]; this lack of efficacy has been ascribed to the feedback activation of EGFR, which ensues as a consequence of BRAF inactivation and leads to EGFR-dependent compensatory signals [58, 59]. The gene discussed is EGFR; the disease is melanoma.