NF1 and malignant peripheral nerve sheath tumor: More than a third of AYAs with MPNST had an NF-1 mutation, which is associated with worse prognosis compared with sporadic MPNST.10,24 Patients with MPNST respond relatively poorly to chemotherapy and those arising in the setting of NF-1 mutations may have inferior response rates.25,26 Loss of the NF-1 protein leads to activation of the RAS signaling pathway; however, therapeutic attempts to target RAS signaling and downstream pathways have had disappointing results.27 Clinical trials evaluating multiagent strategies (such as MEK and mTOR inhibitors) are ongoing and results are awaited.