对于晚期胃癌，目前国际公认的治疗原则是以化疗为主的综合治疗,探索新的药物靶点并进行个体化治疗，是近年来胃癌治疗研究重点。酪氨酸激酶受体c-Met（肝细胞生长因子受体）是治疗晚期胃癌药物最具潜力的靶点之一，但如何实现个体化靶向治疗以及如何减少耐药性等问题尚未解决。申请人在前期研究中发现：c-Met抑制剂可以诱导胃癌细胞系自噬的发生；抑制自噬可以增加胃癌细胞对c-Met抑制剂的敏感性。由此提出自噬在靶向c-Met治疗胃癌中发挥重要作用的科学问题。本课题拟采用体内和体外实验，明确自噬在靶向c-Met治疗中发挥的作用以及c-Met抑制剂诱导胃癌细胞发生自噬的可能分子机制，了解c-Met信号通路与自噬的交互作用，为靶向c-Met通路治疗晚期胃癌以及克服其耐药问题提供理论基础和解决策略。

The international consensus on treatment principal for advanced gastric cancer is comprehensive therapy based on chemotherapy. Now the research for advanced gastric cancer is focusing on to discovering new targets and screening suitable patients for individual treatment. Targeting c-Met (hepatocyte growth factor receptor) to treat advanced gastric cancer is one of the most promising methods. However, it is not clear how to choose right patients and cope with drug resistance. We have found that: c-Met inhibitors could induce autophagy of gastric cancer cells; inhibiting autophagy could increase the sensitivity of gastric cancer cell for c-Met inhibitors. Thus, we suppose that autophagy may play a key role in the treatment of advanced gastric cancer of targeting c-Met. To test this hypothesis, we intend to perform in vitro and in vivo experiments to investigate the role of autophagy in the treatment of advanced gastric cancer of targeting c-Met, further explore the molecular mechanism of autophagy in treatment of gastric cancer. Our study will elucidate the molecular mechanism of autophagy regulated by c-Met and provide theory basis and strategy for targeting c-Met to treat advanced gastric cancer and overcome drug resistance.