Dauricine regulates SAT1 to induce ferroptosis and overcome osimertinib resistance in Non-small cell lung cancer

Targeted tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of lung cancer; however, nearly all patients face the challenge of TKI resistance. Unraveling the molecular mechanisms of TKI resistance and effectively addressing it is a pressing clinical issue. We have successfully established a third-generation TKI-resistant lung cancer cell line and organoids, and identified batatasin alkaloid from 302 traditional Chinese medicines as capable of effectively overcoming osimertinib resistance. Our scientific hypothesis posits that batatasin alkaloid improves osimertinib resistance by modulating ACSL1 to influence lipid peroxidation-induced ferroptosis. This project aims to utilize various lung cancer models to elucidate the relationship between osimertinib resistance and ferroptosis in lung cancer, uncover the specific molecular mechanisms by which batatasin alkaloid regulates ACSL1, and explore the feasibility of batatasin alkaloid in improving osimertinib resistance. This project will unveil novel molecular mechanisms of TKI resistance in lung cancer and explore the application of traditional Chinese medicine in overcoming resistance to targeted therapy for lung cancer.