Figure. Outline of the study (IMAGE)
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A. We have developed a Cldn18-IRES-CreERT2 driver that selectively introduces mutations in mouse gastric epithelium. We have succeeded in establishing a new mouse model (C18-ATK) that reproduces human metastatic gastric cancer, by combining Wnt with Kras or Trp53 mutations reported in human gastric cancer. This mouse model accurately reproduces human advanced gastric cancer and can be an excellent model for gastric cancer research. B. We have developed orthotopic transplantation models using gastric cancer organoids established from gastric cancer tissue of C18-ATK mice. By using these transplantation models, the time needed for analysis can be significantly shortened, and high-quality, large-scale analysis becomes possible. C. The combination of removal of Lgr5+ gastric cancer stem cells and an anticancer drug, 5-fluorouracil, significantly suppressed the progression of gastric cancer. It was suggested that a breakthrough treatment for advanced gastric cancer could be developed by targeting Lgr5+ gastric cancer cells that are also present in human gastric cancer.
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Kanazawa University
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