Melanoma progression and the development of BM are influenced by microenvironmental cues and molecular factors, including mutations in BRAF, NRAS, and PTEN, and activation of the PI3K/AKT (by chemokine ligand CCR4) and JAK/STAT3 pathways.68 CCR4 activation, for instance, triggers PI3K/AKT activation and contributes to the adhesion of primary tumor cells to the brain.73 This evidence concerns the gene PIK3CA and neoplasm.