In the study by Gorges et al., continuous changes of the mutation profiles were detected in CTCs from MEL patients regarding the genes BRAF, NRAS, EGFR, and MAP2K1. Cancer plasticity during targeted therapy has not only been evident from the analysis of cfDNA and CTCs but also from studies of blood-derived extracellular vesicles as previously published by our group. Here, MAP2K1 is linked to melorheostosis.