RAS-ON inhibition overcomes clinical resistance to KRAS G12C-OFF covalent blockade

Key Points

• RAS-ON inhibition effectively overcomes clinical resistance arising against covalent KRAS G12C-OFF blockade across targeted cancer therapies.
• Targeting the active RAS-ON state blocks oncogenic signaling pathways when selective KRAS G12C inhibitors encounter acquired resistance.
• Analysis demonstrates that covalent blockade resistance is mitigated by direct RAS-ON inhibitors, highlighting potential for future therapy.