Kirsten rat sarcoma viral oncogene homolog, G12C mutant (KRAS (G12C))

KRAS (G12C) is a mutant form of the Kirsten rat sarcoma viral oncogene homolog protein, where glycine at position 12 is substituted by cysteine. It is a member of the RAS family of small GTPases, acting as a molecular switch that cycles between inactive GDP-bound and active GTP-bound states to regulate cell proliferation and survival. The G12C mutation leads to impaired GTPase activity, resulting in continuous activation of downstream oncogenic pathways. KRAS G12C is a key driver in various cancers, including non-small cell lung cancer, colorectal cancer, and pancreatic cancer. Recently developed covalent inhibitors, such as sotorasib and adagrasib, target this specific mutant by irreversibly binding to the cysteine residue at position 12, locking the protein in its inactive form and suppressing cancer cell growth. Resistance mechanisms, tumor heterogeneity, and safety concerns such as hepatotoxicity remain major therapeutic challenges[1][2][3].

Other names

KRAS G12CKRAS Gly12CysKRAS p.G12CK-Ras protein, G12C mutant

Covalent binding to cysteine 12 to lock the KRAS G12C mutant in its inactive GDP-bound state Inhibition of downstream signaling pathways such as MAPK and PI3K