Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

Abstract

Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer.

Ferroptosis: emerging roles in lung cancer and potential implications in biological compounds

“…System Xc-is a heterodimeric cell surface amino acid reverse transporter protein, including transmembrane transporter SLC7A11 which is crucial in initiating ferroptosis. Based on current research, the targets of ferroptosis in lung cancer mainly focus on the regulation of antioxidant pathways, among which GPX4 and SLC7A11 are the core targets of GSH-dependent antioxidant pathways ( Xing et al, 2023 ). On the contrary, due to the inherent drawbacks of DHA including poor stability, low water solubility, and short plasma half-life, its therapeutic efficacy is compromised.…”

Analysis of the incidence and influencing factors of abdominal distension in postoperative lung cancer patients in ICU based on real-world data: a retrospective cohort study

“…Available treatments for lung cancer include surgery, chemotherapy, immunotherapy, and radiotherapy [ 3 ]. Surgery is the primary treatment for early-stage lung cancer patients.…”

Revealing prognostic insights of programmed cell death (PCD)-associated genes in advanced non-small cell lung cancer

“…It holds significant potential as a target for drug therapy. Ferroptosis inhibitors could regulate and activate P53 and its downstream genes and further induce ROS accumulation and ferroptosis [ 12 , 13 ]. Ku et al discovered that JI017 can induce cell autophagy and apoptosis by enhancing ROS levels, reducing tumor size in lung cancer.…”