We have also observed that more potent MEK inhibitors such as trametinib have had more than expected toxicity when used off label in plexiform neurofibroma patients perhaps suggesting that there is an optimal level of MEK suppression to allow for antitumor activity without toxicity in MPNST patients that would be lower than the maximally tolerated single agent dose (AB, personal communication). The gene discussed is MAP2K7; the disease is plexiform neurofibroma.