Kirsten rat sarcoma viral oncogene homolog G13C mutant (KRAS G13C)

The Kirsten rat sarcoma viral oncogene homolog G13C mutant (KRAS G13C) is a specific variant of the KRAS gene in which glycine (G) at position 13 is replaced by cysteine (C). KRAS is a small GTPase and signal transduction protein that regulates cell growth, proliferation, and survival. The G13C mutation leads to a constitutively active form of KRAS, driving uncontrolled cell division and tumor formation. KRAS G13C is frequently found in human cancers, including colorectal, lung, and pancreatic tumors, and is associated with differential response to chemotherapy and prognosis. The G13C mutant uniquely impacts cell cycle, differentiation, apoptosis, and cytokine-driven signals, and represents a distinct clinical entity compared to other KRAS mutants. There are no approved direct inhibitors for KRAS G13C, but targeted drug development is ongoing, inspired by advances in inhibitors for other KRAS mutants. KRAS G13C mutation detection is used as a biomarker for patient selection and treatment stratification, although challenges remain due to pathway complexity, toxicity risks, and resistance mechanisms[1][2][3][4][5][6].

Other names

KRAS G13CKRAS Gly13CysKRAS (G13C)[1][2][3][5][6]

Inhibitors would aim to block the constitutive activation of KRAS G13C resulting from impaired GTP hydrolysis, potentially by: - Preventing KRAS-GTP binding - Promoting inactive KRAS conformation - Blocking downstream effector interactions (e.g., PI3K, RAF/MEK/ERK)[2][3][6]