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The c-KIT oncogene is located on chromosome band 4q12 and encodes a type Ill RTK family transmembrane glyco­protein, whose ligand is stem cell factor (SCF). The binding of SCF promotes c-KIT dimerization and transphosphor­ylation, activating downstream signaling pathways involved in proliferation, differentiation, migration, and survival. In human cancer, KRAS gene mutation occurs in nearly 90% of pancreatic cancer, 30-40% of colon cancer, 17% of en­dometrial cancer and 15-20% of lung cancer (mostly NSCLC). Research has found that KRAS mutations are mainly located at four hotspot codons (12, 13, 61, and 146). Codon 12 has the highest mutation frequency among all four hotspot codons, with G12D mutation being the most common, followed by G12V, G12C, and others. Ba/F3 is a mouse pro-8 cell line that relies on interleukin-3 for survival and can also be introduced with exogenous activated ki­nases for growth. Ba/F3 cells are widely used as models for evaluating the efficacy of kinase oncogenes, down­stream signal transduction, and the blocking ability of small molecule kinase inhibitors. We have constructed over 300 stable Ba/F3 point mutant strains and conducted in vivo xenograft experiments on some of them, obtaining good tumorigenic and pharmacological data. In this study, we constructed CDX models using BaF3 c-KIT mutant cell lines and BaF3 KRAS-G12C mutant cell lines. The results showed that the BaF3 mutation tumor models are suitable for the drug discovery of specific point mutation anti-cancer drugs.


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