Activity of direct KRAS(G12C) inhibitors in preclinical models of pediatric cancer.

ABSTRACT: Directly targeting RAS is a promising approach for the treatment of RAS-altered malignancies. Recently, several groups have developed mutation-specific agents such as sotorasib and adagrasib, which directly target KRAS by covalently modifying KRAS(G12C). KRAS is commonly altered in adult malignancies, such as lung, pancreatic, and colorectal adenocarcinomas, but is less commonly altered in pediatric cancers. However, rare pediatric solid tumors harboring K-, H-, or NRAS(G12C) have been observed, including rhabdomyosarcoma and neuroblastoma tumors as well as leukemias. The efficacy of KRAS(G12C) inhibitors in pediatric malignancies is currently unknown, and the ability of these drugs to modify H- and NRAS(G12C) has not been completely characterized. Here, we show that sotorasib, adagrasib,

SUBMITTER: Price HE 

PROVIDER: S-EPMC12776615 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature