Kirsten rat sarcoma viral oncogene homolog (KRAS) proto-oncogene, GTPase (KRAS)

Kirsten rat sarcoma viral oncogene homolog (KRAS) encodes a small GTPase enzyme that acts as a molecular switch within cells. It cycles between an active GTP-bound state and an inactive GDP-bound state to regulate signal transduction through the RAS/MAPK pathway. This signaling controls key cellular processes including proliferation, differentiation, survival, and apoptosis[1][3][5]. Mutations—most commonly at codons 12, 13 or 61—lead to constitutive activation of K-Ras protein function independent of upstream signals. These activating mutations drive uncontrolled cell division and are implicated in many human cancers including lung adenocarcinoma (~15–25% of cases), pancreatic ductal adenocarcinoma (>90%), colorectal carcinoma (~40%), among others[1][3][5][7]. Germline mutations can cause developmental syndromes such as Noonan syndrome. Therapeutically targeting mutant forms of this protein has been challenging due to its structure; however recent advances have led to approved inhibitors for specific mutants like KRAS(G12C). The presence or absence of certain mutations serves both prognostic purposes (often indicating poorer outcomes) and guides therapeutic decisions regarding targeted therapies versus standard treatments[5][7]. In summary: **KRAS** is a critical molecular switch regulating cell fate decisions; when mutated it becomes one of the most important drivers across multiple human cancers[1][3].

Other names

K-RasKRAS2RASKc-Ki-ras2Ki-Ras

Drugs such as sotorasib and adagrasib act as covalent inhibitors that specifically bind to the cysteine residue in the KRAS G12C mutant protein, locking it in an inactive GDP-bound state and thereby inhibiting downstream signaling pathways involved in tumor growth.