Another possibility is to directly target the “rewired phase.” In this phase, in which cells display an almost uniform rewiring response and >80% of tumors react with MITF up-regulation, targeting the rewiring-mechanism produces impressive responses in pre-clinical studies (Smith et al., 2016) Thus, with all the excitement about the latest immunotherapy successes, it should not be forgotten that BRAF and MEK inhibitors produce immediate and impressive results and long-lasting (>4 years) responses are also observed in a number of melanoma patients (Puzanov et al., 2015). This evidence concerns the gene MITF and melanoma.