We validated the finding that Notch1 activation can drive resistance to MAPK pathway inhibitors in BRAF mutant melanomas by evolving resistance to RAF (PLX4720), MEK (AZD6244) and ERK (VX-11E) inhibitors in 6 BRAF mutant melanoma cell lines, ultimately developing 18 pooled and 84 clonal resistant derivatives. Here, BRAF is linked to melanoma.