Although MEK–ERK signaling has not yet been implicated in this response, 22% of SCCs harbour oncogenic mutations in RAS (9% HRAS, 8% NRAS, 5% KRAS: www.sanger.ac.uk/genetics/CGP/cosmic/), raising the intriguing possibility that the BRAF-selective drugs act as tumor promoters in premalignant skin cells harboring existing mutations in RAS and/or activation of upstream components that activate RAS. This evidence concerns the gene HRAS and neoplasm.