Evidently, the effectiveness of peptide delivery systems is context specific and our data shows that CellPorter® has directed intracellular delivery of a novel C-Raf – PDE8A peptide disrupter leading to significant suppression of paradoxical ERK activation in a clinically relevant B-Raf inhibitor resistant human melanoma cell line and an apt xenograft model of the disease. Here, RAF1 is linked to melanoma.