The KRAS G12C mutation obstructs the binding of GAP to KRAS, preventing GTP hydrolysis and keeping G12C-mutant KRAS continuously active. This sustained activation triggers the MAPK and PI3K signaling pathways, fueling the formation of tumors. Drugs like sotorasib and adagrasib directly target KRAS G12C by forming a bond with cysteine 12 in the KRAS-G12C protein’s switch-II pocket. This action locks KRAS in an inactive state, halting cell proliferation. While inhibiting KRAS G12C proves effective against certain lung cancers, it doesn’t impact PI3K signaling. This suggests that alternative pathways unrelated to KRAS-G12C might activate PI3K, contributing to resistance ...
