Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is a group of targeted-drugs which effectively inhibits the growth of tumor cells with sensitive mutations in EGFR. However, the innate and acquired resistance are major obstacles of the efficiency. Autophagy is a highly conserved self-digesting process in cells, which is considered to be associated with cancer development andchemoresistance. The activation of EGFR may regulate autophagy through multiple signal pathways. EGFR-TKIs can induce autophagy, however, the function of the inducted autophagy remains biphasic. On one hand, autophagy induced by EGFR-TKI acts as a cytoprotective response in cancer cells, and autophagy inhibitors can enhance the cytotoxic effects of EGFR-TKI. On the other hand, a high level of autophagy after treatment of EGFR-TKI can also result in autophagic cell death lacking features of apoptosis, and the combination of EGFR-TKI with autophagy inducer might be beneficial. Thus, autophagy regulation represents a promising approach for improving the efficiency of EGFR-TKI in the treatment of cancer patients. Here we summarized the signaling pathways involved in EGFR-TKI induced autophagy, and reviewed the roles of autophagy in the treatment and chemoresistance of EGFR-TKI treatment in lung cancer.
表皮生长因子受体激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor, EGFR-TKI）是一类针对肿瘤细胞中EGFR的异常活化而开发的肿瘤靶向药物，可以有效抑制带有EGFR敏感突变的肿瘤细胞的生长。然而先天性以及获得性耐药严重制约了该类药物的使用。近些年的研究发现自噬（autophagy），作为一个细胞编码的高度保守的应对压力的存活机制，其与肿瘤的发生发展及抗肿瘤药物的耐药密切相关。EGFR的激活可以通过多条通路调控自噬。EGFR-TKI也可以诱导自噬，且自噬在EGFR-TKI的治疗和产生耐药性的过程中发挥着双刃剑的作用：一方面EGFR-TKI诱导的自噬是肿瘤细胞的一个保护机制，联合使用自噬抑制剂可以增强药物的细胞毒性效果；同时还有研究证明EGFR-TKI诱导的高水平自噬可以在凋亡缺陷的细胞中造成自噬性死亡，这种情况下联合使用自噬诱导剂则可能产生更好的效果。因此，针对不同的情况通过调控自噬以提高EGFR-TKI的治疗效果是一个颇具前景的治疗方案。本文对EGFR-TKI和自噬相关的信号通路进行了阐述，并对自噬在EGFR-TKI类药物对肺癌的治疗和耐药中作用的最新研究进展进行了总结，为设计联合方案提高EGFR-TKI的抑制效果，降低耐药性提供线索。.