Thus, as with VAV1 overexpressing A375 cells, Rac1 mutant VRPP3 cells displayed resilience to combined MEK1/2 RNAi depletion coupled with combined BRAFi/MEKi pharmacological inhibition, confirming that a subset of spontaneously BRAFi-resistant V600-mutant melanoma cells also utilize a Rac1-dependent pathway to become drug resistant. Here, MAP2K1 is linked to melanoma.