Ferroptosis in lung cancer: Emerging mechanisms, therapeutic targeting, and immune modulation

Ferroptosis is a form of programmed cell death discovered in recent years, characterized by iron-dependent lipid peroxidation and aberrant accumulation of reactive oxygen species (ROS), ultimately leading to plasma membrane rupture and cellular lysis. Key regulatory mechanisms of ferroptosis include glutathione (GSH) metabolism, iron homeostasis, and the lipid peroxidation related enzyme system. Studies have confirmed that cancer cells generally exhibit higher ROS levels, abnormal metabolic reprogramming and enhanced iron dependency, making them more vulnerable to ferroptosis. Recent research has demonstrated that ferroptosis plays a significant role in the development and progression of various malignancies, including lung cancer. Inducing ferroptosis can not only inhibit tumor growth and proliferation but also remodel the tumor immune microenvironment (TIME), activate anti-tumor immune responses and enhance tumor sensitivity to immunotherapy. Therefore, targeting ferroptosis has emerged as a highly promising novel strategy in lung cancer treatment. This review systematically summarizes the molecular mechanisms and functional roles of ferroptosis in lung cancer progression and discusses potential directions for its therapeutic application, aiming to provide a reference for further research in this field.