Owing to increased mTOR complex signaling mediated by RAS in NF1-deficient mouse and human cells (Dasgupta et al., 2005b; Johannessen et al., 2005), along with early successes in preclinical mouse models of pNF and MPNST (Johannessen et al., 2008; Wu et al., 2012), phase 2 clinical trials with mTOR inhibitor, sirolimus, were initiated for pNF in children, which unfortunately had limited efficacy (Weiss et al., 2014). This evidence concerns the gene MTOR and malignant peripheral nerve sheath tumor.