👤 L Senovilla

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. Show less

In response to some chemotherapeutic agents such as anthracyclines and oxaliplatin, cancer cells undergo immunogenic apoptosis, meaning that their corpses are engulfed by dendritic cells and that tumor cell antigens are presented to tumor-specific CD8(+) T cells, which then control residual tumor cells. One of the peculiarities of immunogenic apoptosis is the early cell surface exposure of calreticulin (CRT), a protein that usually resides in the lumen of the endoplasmic reticulum (ER). When elicited by anthracyclines or oxaliplatin, the CRT exposure pathway is activated by pre-apoptotic ER stress and the phosphorylation of the eukaryotic translation initiation factor eIF2alpha by the kinase PERK, followed by caspase-8-mediated proteolysis of the ER-sessile protein BAP31, activation of the pro-apoptotic proteins Bax and Bak, anterograde transport of CRT from the ER to the Golgi apparatus and exocytosis of CRT-containing vesicles, finally resulting in CRT translocation onto the plasma membrane surface. Interruption of this complex pathway abolishes CRT exposure, annihilates the immunogenicity of apoptosis, and reduces the immune response elicited by anticancer chemotherapies. We speculate that human cancers that are incapable of activating the CRT exposure pathway are refractory to the immune-mediated component of anticancer therapies. Show less