When tovorafenib was combined with pimasertib in vitro, synergy was observed in an NF1-LOF embryonal rhabdomyosarcoma patient-derived xenograft model ex vivo and an NF1-LOF Malignant peripheral nerve sheath tumors (MPNST) cell line in vitro, suggesting that vertical pathway inhibition is needed in the NF1-LOF mutant setting. This evidence concerns the gene NF1 and rhabdomyosarcoma.