In terms of the potential translational value of our study, the following may be considered: (1) reversibility of the phenotypic states that might influence the outcome of rechallenge with BRAFV600/MEK inhibitors as well as effectiveness of novel drug(s) applied either with targeted therapy or sequentially after targeted therapy discontinuation; and (2) the necessity to stratify melanoma patients for new treatment strategies according to specific resistance- or therapy discontinuation-associated phenotypes. This evidence concerns the gene MAP2K7 and melanoma.