Altogether, although we have not uncovered the mechanism by which PLX4032 activated RAF1 in BRAFWT melanoma cells, our data are consistent with the published reports and suggest that PLX4032 may have a different mode of action, which is independent of RAS-GTP because mutant RAF1 R89L that does not bind RAS was also activated to the same degree as its wild-type counterpart. The gene discussed is RAF1; the disease is melanoma.