These RTKs can also activate the phosphatidyl-inositol-3-kinase/AKT pathway, which is active in most melanomas,21 due to the loss of PTEN expression, or activation of PI3KCA or AKT mutation.22, 23, 24, 25, 26, 27 A phase II clinical study by Trunzer et al.28 identified activating MEK1Q56P and MEK1E203K mutations in vemurafenib-resistant melanomas that were not present in pre-treated tumors. Here, PTEN is linked to melanoma.