In lung cancer cell lines and PDX models, aldo-keto reductase family 1 member B1 (AKR1B1) promoted glutathione de novo synthesis by activating signal transducer and activator of transcription 3 (STAT3), leading to ROS scavenging and ultimately to EGFR-TKI drug resistance. This evidence concerns the gene AKR1B1 and lung cancer.