Ferroptosis: A Specific Vulnerability of RAS-Driven Cancers? (original) (raw)
Related papers
Pharmacological Targeting of Ferroptosis in Cancer Treatment
Journal of drug delivery and therapeutics, 2024
____________________________________________________________________________________________________________ A non-apoptotic iron-dependent form of Regulated Cell Death (RCD) known as ferroptosis is brought on by an excess of harmful lipid peroxides and iron overload. Inhibiting the antioxidant defense system results in overwhelming of GSH dependent pathway and building up irondependent Reactive Oxygen Species (ROS) that react with polyunsaturated fatty acids in large quantities can both cause ferroptosis. Recent research has shown that ferroptosis holds a great deal of promise for preventing tumor cell resistance and limiting growth and spread. Emerging evidence also suggests that ferroptosis plays a dual role in human cancer. However, the precise underlying molecular mechanisms and their different role in tumorigenesis are unclear. Therefore, in this review we summarize and briefly present the key pathways of ferroptosis, its dual role as an oncogenic and as a tumor suppressor event in human cancers, paying special attention to the regulation of ferroptosis along with a variety of current medications and naturally occurring substances that may one day be used to target ferroptosis in tumor cells. Thus, addressing this sort of cell death could be seen as a potentially expanding technique in cancer treatment. Consequently, this will offer crucial viewpoints for next research on ferroptosisbased cancer treatment.
Ferroptosis: A New Road towards Cancer Management
Molecules
Ferroptosis is a recently described programmed cell death mechanism that is characterized by the buildup of iron (Fe)-dependent lipid peroxides in cells and is morphologically, biochemically, and genetically distinct from other forms of cell death, having emerged to play an important role in cancer biology. Ferroptosis has significant importance during cancer treatment because of the combination of factors, including suppression of the glutathione peroxidase 4 (Gpx4), cysteine deficiency, and arachidonoyl (AA) peroxidation, which cause cells to undergo ferroptosis. However, the physiological significance of ferroptosis throughout development is still not fully understood. This current review is focused on the factors and molecular mechanisms with the diagrammatic illustrations of ferroptosis that have a role in the initiation and sensitivity of ferroptosis in various malignancies. This knowledge will open a new road for research in oncology and cancer management.
Frontiers of Ferroptosis in Cancer Treatment
Cellular and Molecular Biology
Recent phenomenal advancements in genomic and proteomic technologies and rapid breakthroughs in the interpretation of large gene expression datasets have enabled scientists to comprehensively characterize the gene signatures involved in ferroptosis. Ferroptosis is an iron-dependent form of non-apoptotic cell death that has gained the worthwhile attention of both basic and clinical researchers. Ferroptosis has dichotomous, context-dependent functions both as a tumor suppressor and promoter of carcinogenesis. Essentially, pharmacological modulation of ferroptosis by its induction as well as its inhibition holds enormous potential to overcome drug resistance and to improve the therapeutic potential of chemotherapeutic drugs in a wide variety of cancers.
Cells
Background: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSCC) are two of the most common subtypes of non-small cell lung cancer (NSCLC), with high mortality rates and rising incidence worldwide. Ferroptosis is a mode of programmed cell death caused by lipid peroxidation, the accumulation of reactive oxygen species, and is dependent on iron. The recent discovery of ferroptosis has provided new insights into tumor development, and the clinical relevance of ferroptosis for tumor therapy is being increasingly appreciated. However, its role in NSCLC remains to be explored. Methods: The clinical and molecular data for 1727 LUAD and LUSCC patients and 73 control individuals were obtained from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Gene expression profiles, copy number variations and somatic mutations of 57 ferroptosis-related genes in 1727 tumor samples from the four datasets were used in a univariate Cox analysis and conse...
Ferroptosis: regulated cell death
Archives of Industrial Hygiene and Toxicology
Ferroptosis is a recently identified form of regulated cell death that differs from other known forms of cell death morphologically, biochemically, and genetically. The main properties of ferroptosis are free redox-active iron and consequent iron-dependent peroxidation of polyunsaturated fatty acids in cell membrane phospholipids, which results in the accumulation of lipid-based reactive oxygen species due to loss of glutathione peroxidase 4 activity. Ferroptosis has increasingly been associated with neurodegenerative diseases, carcinogenesis, stroke, intracerebral haemorrhage, traumatic brain injury, and ischemia-reperfusion injury. It has also shown a significant therapeutic potential in the treatment of cancer and other diseases. This review summarises current knowledge about and the mechanisms that regulate ferroptosis.
Ferroptosis: A unique form of iron-dependent regulated cell death and its role in different diseases
World Journal of Biology Pharmacy and Health Sciences
Ferroptosis, a unique, non-apoptotic, iron-dependent, controlled cell death associated with excessive iron accumulation and phospholipid peroxidation. It causes a reduction in cell volume and an increased density of the mitochondrial membrane. This form of controlled cell death is genetically, biochemically, and morphologically unique from other cell deaths, such as apoptosis, uncontrolled necrosis, and necroptosis. Directly or indirectly, alteration of glutathione peroxidase by ferroptosis inducers, through various mechanisms, causes a loss of antioxidant potential and a build-up of lipid reactive oxygen species (ROS) in cells. Inhibition of glutathione peroxidase 4 (GPX-4), system Xc-cystine/glutathione antiporter, and arachidonoyl (AA) peroxidation induces ferroptosis in cells, which can be mediated by the mitochondrial VDAC3, p53 genes, and a variety of additional regulator genes such as HSPB1, CARS, and NFR2. Aside from these, a number of drugs like sorafenib, lanperisone, arte...
Overview of Ferroptosis and Synthetic Lethality Strategies
International Journal of Molecular Sciences, 2021
Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitizes cancer stem cells and tumors that undergo epithelial−mesenchymal transition and are resistant to anticancer drugs or targeted therapy. Therefore, ferroptosis-inducing molecules are attractive new research targets. In contrast, synthetic lethal strategies approach mechanisms and genetic abnormalities that cannot be directly targeted by conventional therapeutic strategies, such as RAS mutations, hypoxia, and abnormalities in the metabolic environment. They also target the environment and conditions specific to malignant cells, have a low toxicity to normal cells, and can be used in combination with known drugs to produce new ones. However, the concept of synthetic lethality has not been w...
How do we fit ferroptosis in the family of regulated cell death?
Cell Death and Differentiation
In the last few years many new cell death modalities have been described. To classify different types of cell death, the term 'regulated cell death' was introduced to discriminate it from 'accidental cell death'. Regulated cell death involves the activation of genetically encoded molecular machinery that couples the presence of some signal to cell death. These forms of cell death, like apoptosis, necroptosis and pyroptosis have important physiological roles in development, tissue repair, and immunity. Accidental cell death occurs in response to physical or chemical insults and occurs independently of molecular signalling pathways. Ferroptosis, an emerging and recently (re)discovered type of regulated cell death occurs through Fe(II)-dependent lipid peroxidation when the reduction capacity of a cell is insufficient. Ferroptosis is coined after the requirement for free ferrous iron. Here, we will consider the extent to which ferroptosis is similar to other regulated cell deaths and explore emerging ideas about the physiological role of ferroptosis.