Kirsten rat sarcoma virus oncogene (KRAS) (KRAS)

Kirsten rat sarcoma virus oncogene (KRAS) is a member of the RAS family of small GTPases that functions as a molecular switch in signal transduction pathways (UniProt P01116). It cycles between an active GTP-bound state and an inactive GDP-bound state to regulate essential cellular processes such as growth, proliferation, and survival (NCBI Gene 3845). KRAS relays signals from extracellular growth factors to downstream effector pathways, most notably the Raf-MEK-ERK (MAPK) and PI3K-AKT-mTOR pathways (PMID: 32946088). Mutations in the KRAS gene, particularly at codons 12, 13, or 61, impair the intrinsic GTPase activity and lead to constitutive activation, which drives the development and progression of various malignancies (PMID: 34161702). KRAS mutations are highly prevalent in pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer. While long considered undruggable, the discovery of a targetable switch II pocket has led to the approval of covalent inhibitors specifically targeting the KRAS G12C mutation, such as sotorasib and adagrasib, marking a significant milestone in precision oncology (FDA Lumakras/Krazati labels).

Other names

KRAS2RASK2KI-RASC-K-RASK-RAS2AK-RAS2BK-RAS4AK-RAS4BGTPase KRasv-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

Covalent inhibition of the KRAS G12C mutant protein by binding to the switch II pocket, locking it in the inactive GDP-bound state and preventing downstream signaling (PMID: 32946088; FDA Lumakras Label).