Different mechanisms of acquired therapy resistance to either monotherapy with BRAFi or combination treatment could be identified in melanoma [8,13,14,15]: In response to BRAFi, reactivation of the mitogen activated protein kinase (MAPK) pathway, e.g., due to switching among BRAF, ARAF and CRAF isoforms, and enhanced insulin like growth factor (IGF)-IR/PI3K signaling occurred [13]. Here, WNK2 is linked to melanoma.