In a panel of skin melanoma cell lines with differing MAPK and p53 mutation status, specific siRNA toward IGF-1R downregulates the receptor and all its signaling in a balanced manner, while IGF-1R targeting by small molecule Nutlin-3 parallels receptor degradation with a transient biased pERK1/2 activity, with both strategies synergizing with MEK1/2 inhibition (89, 90). This evidence concerns the gene MAP2K1 and cutaneous melanoma.