Several genetic and environmental factors increase gastric cancer (GC) risk, with Helicobacter pylori being the main environmental agent. GC is thought to emerge through a sequence of morphological changes that have been elucidated on the molecular level. New technologies have shed light onto pathways that are altered in GC, involving mutational and epigenetic changes and altered signaling pathways. Using various new model systems and innovative approaches, the relevance of such alterations for the emergence and progression of GC has been validated. Here, we highlight the key strategies and the resulting achievements. A major step is the characterization of epithelial stem cell behavior in the healthy stomach. These data, obtained through new reporter mouse lines and lineage tracing, enabled insights into the processes that control cellular proliferation, self-renewal, and differentiation of gastric stem cells. It has become evident that these cells and pathways are often deregulated in carcinogenesis. Second, insights into how H pylori colonizes gastric glands, directly interacts with stem cells, and alters cellular and genomic integrity, as well as the characterization of tissue responses to infection, provide a comprehensive picture of how this bacterium contributes to gastric carcinogenesis. Third, the development of stem cell– and tissue-specific reporter mice have driven our understanding of the signals and mutations that promote different types of GC and now also enable the study of more advanced, metastasized stages. Finally, organoids from human tissue have allowed insights into gastric carcinogenesis by validating mutational and signaling alterations in human primary cells and opening a route to predicting responses to personalized treatment.

几种遗传和环境因素会增加胃癌 (GC) 的风险，幽门螺杆菌是主要的环境因素。GC被认为是通过一系列已在分子水平上阐明的形态变化而出现的。新技术揭示了 GC 中改变的途径，包括突变和表观遗传变化以及改变的信号通路。使用各种新模型系统和创新方法，已经验证了这些改变与 GC 的出现和进展的相关性。在这里，我们强调关键战略和由此产生的成就。一个重要步骤是表征健康胃中的上皮干细胞行为。这些数据是通过新的报告小鼠系和谱系追踪获得的，有助于深入了解控制细胞增殖、自我更新和胃干细胞分化的过程。很明显，这些细胞和途径在致癌过程中经常失调。二、洞察方式H pylori定植于胃腺，直接与干细胞相互作用，改变细胞和基因组的完整性，以及组织对感染的反应的表征，提供了这种细菌如何促进胃癌发生的全面画面。第三，干细胞和组织特异性报告小鼠的发展推动了我们对促进不同类型 GC 的信号和突变的理解，现在也使研究更先进的转移阶段成为可能。最后，来自人体组织的类器官通过验证人类原代细胞的突变和信号变化，并开辟了一条预测个性化治疗反应的途径，可以深入了解胃癌的发生。