Kirsten rat sarcoma viral oncogene homolog p.G12C mutant (KRAS G12C)

Kirsten rat sarcoma viral oncogene homolog p.G12C mutant (KRAS G12C) refers to a specific point mutation in the KRAS gene where glycine at position 12 is replaced by cysteine. This alteration results in constitutive activation of the encoded small GTPase enzyme, leading to persistent downstream signaling that promotes uncontrolled cell proliferation and survival—key features driving tumorigenesis. The KRAS G12C mutation is most commonly found in non-small cell lung cancer (~13% of cases), but also occurs less frequently in colorectal (~3%) and pancreatic cancers (~1–2%). Historically considered "undruggable," recent advances have led to FDA-approved covalent inhibitors specifically targeting this mutant protein. Testing for this biomarker guides patient selection for these therapies and informs prognosis due to its association with aggressive disease biology and potential drug resistance mechanisms arising from additional genetic alterations within tumors[1][2][5][6].

Other names

KRAS G12CKRas^G12C^KRAS glycine-to-cysteine mutation at codon 12Mutant KRas (Gly12Cys)

Drugs targeting this molecule act as covalent inhibitors, binding irreversibly to the mutant cysteine residue at position 12. This blocks the aberrant signaling activity of the mutant protein that drives tumor growth.