Zhang Qicheng, Xu Ke
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zhongguo Fei Ai Za Zhi. 2016 Sep 20;19(9):607-14. doi: 10.3779/j.issn.1009-3419.2016.09.09.
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.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）是一类靶向药物，可有效抑制具有EGFR敏感突变的肿瘤细胞生长。然而，原发性和获得性耐药是影响其疗效的主要障碍。自噬是细胞内一种高度保守的自我消化过程，被认为与癌症发展和化疗耐药有关。EGFR的激活可能通过多种信号通路调节自噬。EGFR-TKIs可诱导自噬，然而，诱导的自噬功能仍然具有双重性。一方面，EGFR-TKI诱导的自噬在癌细胞中起细胞保护作用，自噬抑制剂可增强EGFR-TKI的细胞毒性作用。另一方面，EGFR-TKI治疗后高水平的自噬也可导致缺乏凋亡特征的自噬性细胞死亡，EGFR-TKI与自噬诱导剂联合使用可能有益。因此，自噬调节是提高EGFR-TKI治疗癌症患者疗效的一种有前景的方法。在此，我们总结了EGFR-TKI诱导自噬所涉及的信号通路，并综述了自噬在EGFR-TKI治疗肺癌的过程及化疗耐药中的作用。
