Together, these analyses revealed a spectrum of heterogeneities in melanoma differentiation state that corresponded to two previously described but distinct ways through which cells may tolerate the effect of Braf/Mek inhibition: (1) incomplete inhibition of the MAPK pathway (as seen in AxlHigh cells), and (2) reduced requirement for MAPK signaling (as seen predominantly in NgfrHigh/AxlLow cells). Here, MAP2K7 is linked to melanoma.