We first used the melanoma cell line NPA cell, a cell clone derived from the melanoma cell line M14 cell [34], and inhibitors of the MAPK and PI3K/Akt pathways to test the therapeutic potential for melanoma of dully targeting the two pathways to induce potent cell inhibition coupled with thyroid iodide-handling gene expression for potential radioiodide treatment. This evidence concerns the gene PIK3CA and melanoma.