Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C)

Kirsten rat sarcoma viral oncogene homolog (KRAS) is a gene encoding a small GTPase protein, K-Ras, which plays a central role in cell signaling pathways that regulate proliferation, differentiation, and survival. The G12C mutation refers specifically to a substitution at codon 12 where glycine (G) is replaced by cysteine (C). This mutation locks KRAS in an active state, leading to continuous activation of downstream signaling pathways such as RAF-MEK-ERK and PI3K-AKT-mTOR. KRAS-G12C is a therapeutic target in several cancers, particularly NSCLC, and is inhibited by covalent inhibitors like sotorasib and adagrasib. Resistance is a major challenge.

Other names

KRAS G12C mutantKRAS G12C variant

Covalent binding and inhibition of mutant KRAS-G12C protein.