AZD9291是对EGFR敏感突变和T790M耐药突变均有明显疗效的高选择性三代EGFR-TKI，但同样面临耐药窘境。研究表明，保护性自噬会导致TKI耐药。我们前期研究发现，糖酵解酶HK2能通过调控糖酵解促进自噬从而导致AZD9291耐药。经典降糖药Metformin可抑制自噬。我们推测，其机制是通过抑制HK2与mTORC1结合减弱自噬，并逆转AZD9291耐药。本研究拟探讨Metformin抑制HK2与mTORC1结合的机制及对自噬的影响在逆转AZD9291耐药中的作用。以期提供延缓AZD9291耐药的联合用药方案。

AZD9291, a high selectivity third-generation epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI) with activities against both EGFR sensitizing resistance and T790M resistance mutation, is also facing resistance.Research shows that protective autophagy causes resistance to TKI. In our previous research, we found that the glycolytic enzyme HK2 can promote autophagy by regulating the glycolysis resulting in AZD9291 resistance.The classic antidiabetic medications Metformin can inhibit autophagy.We speculate it is diminished by inhibiting HK2 combined with mTORC1, and reverses AZD9291 resistance.This study intends to explore the mechanism in order to provide combination scheme to delay AZD9291 resistance.