Manipulating labile iron to enhance the therapeutic response of NSCLC to chemoradiation therapy

Lung cancer is one of the most life-threatening and deadliest cancers in the world. Risk factors related to lung cancer include smoking history, second-hand exposure to tobacco smoke, radiation exposure, environmental pollution such as radon gas, asbestos, carcinogens, and other toxins, and family medical history. Although recent developments in the science, technology, and methods of treatment have led to improved response to therapies for treating lung cancer, the 5-year patient survival rate remains low. Standards of care (SOC) for advanced stages of lung cancer patients include chemotherapy, radiation, and immunotherapy. In this study, we aimed to develop metabolically targeted therapies to improve the SOC of lung cancer patients, especially the most common type of non-small lung cancer (NSCLC) by exploiting alterations in the iron metabolism of cancer cells. Since NSCLC tissue is known to possess an increased dependence on iron metabolism compared to its normal counterparts, we have implemented iron chelation therapy to target available iron in NSCLC cells. Our iron chelation study utilized the conditional overexpression of the iron storage protein ferritin (Ft) as well as an FDA-approved iron-chelating agent, deferoxamine (DFO), which has shown promising results to improve chemo-radiation therapy in vitro and in vivo model systems. Further application of this work will hopefully improve the current therapeutic outcome of lung cancer patients and increase the overall survival.