MEKi are effective in treating people with NF1-associated clinical manifestations, including pNF (Gross et al. 2020) and low-grade gliomas (Fangusaro et al. 2019), but have demonstrated limited activity in preclinical models of NF1-MPNST (Wang et al. 2021; Wang et al. 2020). Here, NF1 is linked to malignant peripheral nerve sheath tumor.