To test whether these drugs act on the expected pathways in inhibitor-treated nf1/pten-mutant melanomas, we analyzed treated tumors by IHC, observing that treatment with the MEK inhibitor trametinib leads to a reduction in pERK levels (Fig. 4a, b), as expected; while levels of pAKT and pS6 are increased (Fig. 4a, c, d), reflecting the loss of RAS-MEK-MAPK-mediated cross-inhibition of PI3K-AKT-mTOR signaling [27]. Here, NF1 is linked to melanoma.