Later analyses of genetic data from multiple clinical trials of BRAF inhibitors in melanoma found putative resistance-causing mutations in 58–74% of progressive tumors and confirmed the reactivation of the RAS/MAPK pathway itself as the major cause of resistance to targeted therapy (Johnson et al., 2015b; Shi et al., 2014; Van Allen et al., 2014). Here, BRAF is linked to melanoma.