Ferroptosis and Radiotherapy in Lung Cancer

Background: Lung cancer (LC) is a leading cause of cancer mortality worldwide. While radiotherapy (RT) has been a lasting cornerstone of LC management, there are concerns due to tumor radioresistance and unintended damage to surrounding healthy tissue. Ferroptosis is a recently described mechanism of programmed cell death which has potential to serve as a complementary adjunct to facilitate RT-based LC treatment. Objectives: This review is a comprehensive overview of ferroptosis in the broader context of synergism with RT for LC. Summary: Ferroptosis is essentially driven by intracellular iron overload, which drives the formation of reactive oxygen species, ultimately resulting in membrane instability and cell death. LC lines have been shown to exhibit a heterogeneous mix of pro- and anti-ferroptotic changes. RT shows promise as a potential ferroptosis inducer, especially when complemented with pharmacologic agents such as erastin. Conclusions: Ferroptosis represents a promising modern adjunct to a traditional therapeutic strategy. Future work should focus on rigorous dosage standards to avoid unintended toxicity, repurposing of currently available drugs into ferroptosis inducers, and establishment of safety protocols to begin the pathway towards clinical studies.