Kirsten rat sarcoma viral oncogene homolog (G12V mutant) (KRAS G12V)

KRAS G12V refers to a specific mutant form of the Kirsten rat sarcoma viral oncogene homolog, a small GTPase enzyme (hydrolase) acting as a molecular switch in signal transduction pathways responsible for cell proliferation, differentiation, and survival[5][6]. The G12V indicates a glycine-to-valine substitution at position 12, resulting in constitutive activation and resistance to intrinsic GTPase activity, which drives oncogenic signaling independently of upstream cues[6]. KRAS G12V mutations are prevalent in several human cancers, including lung, colorectal, and pancreatic carcinoma[5], and are associated with aggressive tumor phenotypes and specific patterns of metastasis (such as pleuropericardial spread)[6]. This mutation makes the KRAS G12V protein an important, though historically difficult, therapeutic target for both direct inhibition and immunological targeting (e.g., neoantigen-specific TCR adoptive cell therapies)[4][8]. While direct inhibitors are still investigational, research has shown successful blockade using engineered peptides and promising immunotherapeutic approaches targeting the mutant protein. Its presence guides targeted therapy and biomarker-driven selection in cancer treatment paradigms.

Other names

K-Ras G12VKRASG12VKRAS (G12V)KRAS4B G12VK-Ras 2 G12V mutant

Direct inhibition of mutant KRAS G12V protein (investigational peptides/proteins) Downstream signaling blockade (e.g., RAF/MEK/ERK pathway inhibitors) Mutation-specific immune recognition by engineered TCRs[4]