PTEN and melanoma: The dysregulated activation of the AKT pathway occurs in around 70% of total melanomas, which is the result of AKT3 amplification and PTEN loss by epigenetic silencing or deletion as previously described.41,42 Generally, the activation of the AKT pathway is initiated by activated phosphoinositide 3-kinase (PI3K) after the stimulation by exogenous growth factors, followed by increased generation of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3) that can promote the translocation of AKT to the plasma membrane for its subsequent phosphorylation and activation.