Aspc-1-KRAS-G12D-L56V-E62Q-KI Cell Line

The KRAS gene, encoding the Kirsten rat sarcoma viral oncogene homolog, is a member of the RAS family of small GTPases. KRAS plays a crucial role in transmitting signals from cell surface receptors to downstream effectors, primarily through the MAPK/ERK and PI3K/AKT signaling pathways. These pathways regulate various cellular processes, including proliferation, differentiation, survival, and apoptosis.The KRAS-G12D-E62Q mutation represents a rare but highly aggressive double mutation in the KRAS oncogene, combining the common G12D substitution with an additional glutamine substitution at position 62 (E62Q). The G12D mutation impairs GTP hydrolysis, locking KRAS in a constitutively active GTP-bound state, while the E62Q mutation, located in the switch II region, further enhances signaling output by promoting a GTP-bound conformation and potentially altering effector binding. This synergistic effect leads to hyperactivation of downstream pathways like MAPK and PI3K, resulting in enhanced tumorigenesis, increased metastatic potential, and resistance to therapy. This variant has been identified in pancreatic, colorectal, and non-small cell lung cancers, where it is associated with a poor prognosis. Its unique structural features present a challenge but also a potential vulnerability for the development of mutant-specific KRAS inhibitors, making it a subject of intense research following the success of G12C-targeted drugs.