The Role of Ferroptosis in Lung Cancer and Its Immunotherapeutic Targeting Strategy

Ferroptosis, an iron-dependent mode of cell death, exhibits unique potential in lung cancer therapy through the mechanisms of lipid peroxidation accumulation and glutathione peroxidase 4 (GPX4) inactivation. Lung cancer cells are highly sensitive to ferroptosis due to metabolic abnormalities and elevated levels of reactive oxygen species (ROS), in which the targeted inhibition of GPX4 and the regulation of the Nrf2 signaling pathway become key molecular mechanisms. Ferroptosis not only directly induces tumor cell death, but also significantly enhances the immunotherapeutic effect by releasing tumor antigens and remodeling the immunosuppressive microenvironment. However, the non-specific toxicity of ferroptosis inducers, drug resistance due to tumor heterogeneity, and the efficiency of targeted delivery still need to be addressed. In this paper, we will systematically explore the synergistic mechanism of ferroptosis and immunotherapy, and propose that the development of microenvironment-responsive drug delivery systems and combined therapeutic strategies is the direction of future breakthroughs. It provides a new idea for ferroptosis-targeted therapy to overcome immunotherapy resistance in lung cancer, but its clinical translation needs to be continuously explored in the in-depth analysis of the mechanism and technological innovation.