Establishment of KRAS G12C mutant brain metastasis models for preclinical evaluation of KRAS G12C targeted anti-cancer therapy

Explore a comprehensive KRAS biochemical assay platform developed by ChemPartner that encompasses in vitro biochemical assays, 2D and 3D cell-based models, and in vivo models to study KRAS G12C inhibitors. These models were validated using AMG 510. The preliminary results demonstrate that AMG 510 potently inhibits the biological activity of the KRAS G12C mutation in NCI-H358-Luc cells. Additionally, AMG 510 appears to penetrate the blood-brain barrier and exhibit therapeutic efficacy against KRAS G12C brain metastatic tumors.

These models represent powerful tools for clinically relevant assessment of the efficacy of novel KRAS G12C inhibitors. Furthermore, they can be expanded for research on other KRAS mutations associated with brain metastases, or the development of new inhibitors.