SOS1 and Noonan syndrome: Activating mutationsof SOS1 are found in ∼1% of lung adenocarcinomasand uterine carcinomas and at lower frequencies in other cancer types.20 Furthermore, these mutations have been reportedin other RASopathies such as hereditary gingival fibromatosis (HGF)21,22 and Noonan’s syndrome.23−25 The catalytic site of SOS1 hasa well-defined binding pocket adjacent to the KRAS:SOS1 interface;thus, disrupting the SOS1:KRAS protein–protein interaction(PPI) with an SOS1 binder is a compelling strategy to help treat KRAS-drivencancers.