SOX2 promotes radiotherapy resistance in lung cancer via HSP70-mediated autophagy

Lung cancer is a highly prevalent malignant tumor, and radiotherapy serves as one of its primary treatment modalities. However, radiotherapy resistance significantly limits therapeutic efficacy. SOX2 has been implicated in treatment resistance across multiple cancer types, yet its role in radiotherapy resistance in lung cancer remains unclear. In this study, we observed that SOX2 is upregulated in lung cancer, and its knockdown enhances the radiosensitivity of lung cancer cells. Further experiments revealed that SOX2 promotes HSP70 expression and that radiotherapy resistance in lung cancer cells is associated with autophagy. Mechanistically, SOX2 functions as a transcription factor to regulate HSP70 transcription, thereby mediating autophagy and consequently reducing radiosensitivity. These results indicate that targeting SOX2 could be a promising strategy to overcome radiotherapy resistance in lung cancer.