biostudies-literatureGross AMIntramural NIH HHSNHLBI NIH HHS866-876https://www.ebi.ac.uk/biostudies/studies/S-EPMC7456498biostudies-literatureUnknown182(4)RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1-related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selAmerican journal of medical genetics. Part AAdvancing RAS/RASopathy therapies: An NCI-sponsored intramural and extramural collaboration for the study of RASopathies.PMC7456498ZIA CP010144R35 HL135742Schill LHernandez ERRauen KAMcCormick FWidemann BCGross AMLoh MLMorrison DKGripp KWFrone MLegius EStewart DRSchoyer LSavage SAYohe MEGelb BDBiesecker LGMartin SStronach BEsposito DWolters PLZand DfalseAdvancing RAS/RASopathy therapies: An NCI-sponsored intramural and extramural collaboration for the study of RASopathies.RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1-related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, sel2020-01-01T00:00:00Z2020 Apr2025-04-25T23:39:58.8Z2020-09-03T07:01:01ZS-EPMC74564983191357610.1002/ajmg.a.61485