Previous study from our laboratory has demonstrated that ESI can induce cell apoptosis through ROS-dependent DNA damage and antitumor inflammation factor pathway.10 In this study, the unexpected finding that ESI could induce protective autophagy through Nrf2-p62-keap1 feedback loop to sustain lung cancer cell survival, suggests that blockade of this feedback loop in combination with ESI is a promising strategy for lung cancer therapy. This evidence concerns the gene KEAP1 and lung cancer.