biostudies-literatureHebron KEIntramural NIH HHSAlex&apos;s Lemonade Stand Foundation for Childhood CancerNational Cancer InstituteNCI NIH HHS472-487https://www.ebi.ac.uk/biostudies/studies/S-EPMC9852065biostudies-literatureUnknown29(2)<h4>Purpose</h4>PAX-fusion negative rhabdomyosarcoma (FN RMS) is driven by alterations in the RAS/MAP kinase pathway and is partially responsive to MEK inhibition. Overexpression of IGF1R and its ligands is also observed in FN RMS. Preclinical and clinical studies have suggested that IGF1R is itself an important target in FN RMS. Our previous studies revealed preclinical efficacy of the MEK1/2 inhibitor, trametinib, and an IGF1R inhibitor, BMS-754807, but this combination was not pursued clinically due to intolerability in preclinical murine models. Here, we sought to identify a combination of an MEK1/2 inhibitor and IGF1R inhibitor, which would be tolerated in murine models and effective in both cell line and patient-derived xenograft models of RAS-mutant FN RMS.<h4>Experimental design</hClinical cancer research : an official journal of the American Association for Cancer ResearchThe Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models.PMC9852065R37 CA262657R21 CA267515HHSN261201500003IR01 CA255232HHSN261201500003CZIA BC011804Kedei NKim AChen JQRoth JSAwasthi PLei HJames APeer CJWan XShern JFVaseva AVDifilippantonio SHall MDFrye WJERobey RWHebron KERobinson CMEdmondson EFLiewehr DJChen LSun WStauffer SButcher DFigg WDIsanogle KASmith RKortum RLKhan JSealover NEYohe MELuo XPerkins OLShankarappa PBarr FGfalseThe Combination of Trametinib and Ganitumab is Effective in RAS-Mutated PAX-Fusion Negative Rhabdomyosarcoma Models.<h4>Purpose</h4>PAX-fusion negative rhabdomyosarcoma (FN RMS) is driven by alterations in the RAS/MAP kinase pathway and is partially responsive to MEK inhibition. Overexpression of IGF1R and its ligands is also observed in FN RMS. Preclinical and clinical studies have suggested that IGF1R is itself an important target in FN RMS. Our previous studies revealed preclinical efficacy of the MEK1/2 inhibitor, trametinib, and an IGF1R inhibitor, BMS-754807, but this combination was not pursued clinically due to intolerability in preclinical murine models. Here, we sought to identify a combination of an MEK1/2 inhibitor and IGF1R inhibitor, which would be tolerated in murine models and effective in both cell line and patient-derived xenograft models of RAS-mutant FN RMS.<h4>Experimental design</h2023-01-01T00:00:00Z2023 Jan2026-06-03T01:17:35.842Z2025-04-06T01:17:26.487ZS-EPMC98520653632200210.1158/1078-0432.ccr-22-164610.1158/1078-0432.CCR-22-1646