BRAF and melanoma: Given the presence of numerous inter-related treatment targets (Figure 5), simultaneous targeting of the Ras/RAF/MAPK/ERK pathway and/or the PI3K/AKT/mTOR pathway with targeted therapy such as a MEK or BRAF inhibitor in melanoma, and inhibition of the renin–angiotensin system, or direct inhibition of PRR, may result in more effective suppression of these overactive pathways.