The mechanistic effect of sirtuin 2 inhibition on melanoma cell resistance may involve the epidermal growth factor receptor (EGFR), which we previously found to be directly regulated by SIRT2 in melanoma cells [9], and a decrease in AKT-RAF-ERK1/2 (protein B kinase–RAF kinase-extracellular signal-regulated kinase 1/2) signaling phosphorylation. Here, MAPK3 is linked to melanoma.