Since the first FDA-approved drug vemurafenib for treating BRAF V600E melanomas, 50–70% of advanced melanoma patients with BRAF V600E mutation had clinically benefited from BRAF inhibitors.7,8 However, all these BRAF inhibitors are not effective against cancers without BRAF V600E mutation because of the paradoxical activation of MAPK signaling pathway. The gene discussed is BRAF; the disease is cancer.