Although evidence that the PI3K/AKT pathway plays a role in melanoma initiation has been demonstrated in functional experiments (reviewed in [88]), studies comparing the levels of PTEN in primary versus metastatic melanomas suggest that PTEN inactivation, the predominant driver of aberrant PI3K/AKT activity in melanoma, is a late event [89,90]. Here, AKT1 is linked to metastatic melanoma.