On the other hand, BRAFi also activates local fibroblasts through a paradoxical stimulation of the MAPK pathway that confers CAFs with the ability to deposit a fibronectin-enriched matrix leading to the activation of pro-survival pathways in melanoma cells through integrin β1, focal adhesion kinase (FAK), and Src signaling [88,89], suggesting that residual disease can be supported by factors deriving from deregulated and fibrotic-like ECM triggered by targeted therapies. This evidence concerns the gene FN1 and melanoma.