Broadening horizons: the role of ferroptosis in cancer

Chen, Xin; Kang, Rui; Kroemer, Guido; Tang, Daolin

doi:10.1038/s41571-020-00462-0

Cited by 1,349 publications

(908 citation statements)

References 183 publications

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“…Ferroptosis is implicated in many pathological conditions of iron overload, including cancer (Chen et al, 2020a;Conrad et al, 2020;. On the one hand, ferroptosis caused by small molecule compounds can inhibit tumor growth in mouse models.…”

Section: Ferroptosis In Diseasesmentioning

confidence: 99%

Characteristics and Biomarkers of Ferroptosis

Chen

Comish

Tang

et al. 2021

Front. Cell Dev. Biol.

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217

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The induction and consequences of regulated cell death (RCD) are accompanied by changes in gene and protein expression, biochemical pathways, as well as cell morphology and size. Such RCDs have a significant impact on development, tissue homeostasis, and the occurrence and progression of disease. Among different forms of RCD, ferroptosis appears to be the main cause of tissue damage driven by iron overload and lipid peroxidation. In fact, the dysfunctional ferroptotic response is implicated in a variety of pathological conditions and diseases, such as neurodegenerative diseases, tissue ischemia-reperfusion injury, tumorigenesis, infections, and immune diseases. Ferroptotic response can be fine-tuned through various oxidative stress and antioxidant defense pathways, coupling with metabolism, gene transcription, and protein degradation machinery. Accordingly, a series of ferroptosis inducers or inhibitors targeting redox- or iron metabolism-related proteins or signal transduction have been developed. Although this kind of RCD has recently attracted great interest in basic and clinical research, detecting and monitoring a ferroptotic response still faces challenges. In this mini-review, we not only summarize the latest knowledge about the characteristics of ferroptosis in vitro and in vivo, but also discuss the specificity and limitations of current biomarkers of ferroptosis.

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Section: Ferroptosis In Diseasesmentioning

confidence: 99%

Characteristics and Biomarkers of Ferroptosis

Chen

Comish

Tang

et al. 2021

Front. Cell Dev. Biol.

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217

132

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“…Ferroptosis, a completely new form of regulated cell death, was first reported in 2012 (Dixon et al, 2012). In the past several years, researchers worldwide have had great interest in studying ferroptosis (Chen et al, 2021). Ferroptosis is an iron-dependent mode of programmed cell death characterized by the accumulation of lipid peroxides.…”

Section: Introductionmentioning

confidence: 99%

Construction and External Validation of a Ferroptosis-Related Gene Signature of Predictive Value for the Overall Survival in Bladder Cancer

Liu

Meng

et al. 2021

Front. Mol. Biosci.

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Purpose: To identify whether ferroptosis-related genes play predictive roles in bladder cancer patients and to develop a ferroptosis-related gene signature to predict overall survival outcomes.Materials and Methods: We downloaded the mRNA expression files and clinical data of 256 bladder samples (188 bladder tumour and 68 nontumour samples) from the GEO database and 430 bladder samples (411 bladder tumour and 19 nontumour samples) from the TCGA database. A multigene signature based on prognostic ferroptosis-related genes was constructed by least absolute shrinkage and selection operator Cox regression analysis in the GEO cohort. The TCGA cohort was used to validate the ferroptosis-related gene signature. Next, functional enrichment analysis, including both Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses, was performed to elucidate the mechanism underlying the signature. The ssGSEA scores of 16 immune cells and 13 immune-related pathway activities between the high-risk and low-risk groups were also analysed in our study.Results: Thirty-three (67.3%) ferroptosis-related genes were differentially expressed between bladder tumour samples and nontumour samples in the GEO cohort. The intersection of prognostic ferroptosis-related genes and differentially expressed genes identified four prognostic targets, including ALOX5, FANCD2, HMGCR and FADS2. The least absolute shrinkage and selection operator Cox regression successfully built a 4-gene signature: risk score value = esum (each gene’s normalized expression * each gene’s coefficient). Univariate and multivariate Cox regression analyses were performed in both the GEO and TCGA cohorts to test the independent prognostic value of the 4-gene risk signature. Multivariate Cox regression analysis in the GEO cohort identified age (p < 0.001), grade (p = 0.129) and risk score (p = 0.016) as independent prognostic predictors for overall survival. Multivariate Cox regression analysis in the TCGA cohort also identified age (p = 0.002), stage (p < 0.001) and risk score (p = 0.006) as independent prognostic predictors for overall survival. The type II IFN response was determined to be significantly weakened in the high-risk group in both the GEO and TCGA cohorts.Conclusion: We successfully built a ferroptosis-related gene signature of significant predictive value for bladder cancer. These results suggest a novel research direction for targeted therapy of bladder cancer in the future.

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“…Besides this, as ferroptosis is iron-dependent form of cell death, which is totally different from apoptosis, necrosis, or pyroptosis, thus the combinations with ferroptotic reagents have the opportunity to circumvent the chemoresistance of apoptosis-inducing chemotherapy drugs and improve the outcomes ( Friedmann-Angeli et al, 2019 ; Liang et al, 2019 ). At present, growing preclinical evidence suggests that ferroptosis-induced cell death was able to prevent emergence of acquired resistance in several chemotherapy drugs, such as lapatinib, trametinib, and erlotinib, and tumor cells selected for drug resistance exhibit the EMT phenotype (characterized by downregulation of epithelial markers and loss of intercellular junctions) ( Sun et al, 2016 ; Friedmann-Angeli et al, 2019 ; Chen et al, 2021 ). Based on current data, targeting ferroptosis is a promising approach to overcome tumor resistance and will certainly be one of the most exciting research hotspots in cancer chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Emerging evidence indicates that multiple molecules and signaling pathways associated with oxidative stress have been linked to regulation of ferroptotic progress ( Wang et al, 2020 ). Accumulation of free iron and that of toxic lipid peroxides are the two major hallmarks of ferroptosis, which is different from other types of cell death ( Chen X. et al, 2020 ; Chen et al, 2021 ).…”

Section: Introductionmentioning

confidence: 94%

Global Research Trends of Ferroptosis: A Rapidly Evolving Field With Enormous Potential

Wang

Tong

et al. 2021

Front. Cell Dev. Biol.

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Background: Ferroptosis is a newly proposed form of programmed cell death, and accumulating evidence suggests that it plays an essential role in the development of multiple diseases, especially cancers and neurodegenerative diseases. Since officially named in 2012, research on ferroptosis has grown rapidly. There are previous reviews focused on the research progress of ferroptosis from a certain aspect, but no bibliometric studies summarizing this field as a whole. This study aimed to assess the scientific output and activity regarding ferroptosis research from a global perspective.Methods: Publications related to ferroptosis from 2012 to 2020 were identified and selected from the Web of Science Core Collection. Excel 2019 and GraphPad Prism 8.0 was used to analyze quantitative variables including number of publications and citations, H-index, and journal citation reports. VOS viewer and CiteSpace were used to perform co-authorship, co-citation, and co-occurrence analysis of countries/institutes/authors/keywords.Results: A total of 1,285 publications on ferroptosis research were identified. The literature on ferroptosis had been continuously growing since 2012, and the expansion might continue at a rapid pace in the following years. China contributed the greatest proportion (43.74%) of ferroptosis publications, and the United States ranked first in the number of citation frequency (20,980 times) and H-index (70). B. R. Stockwell, D. L. Tang, and R. Kang were key researchers. The journal Cell Death Disease published the highest number of articles, with 42 articles. All the keywords could be divided into two clusters: cluster 1 (pathway and mechanism) and cluster 2 (treatment and effect). In terms of potential hotspots, keywords with the strong bursts and still ongoing recently were “neurodegeneration” (2017–2020), “chemotherapy” (2017–2020), “NF-kappa B” (2017–2020), and “photodynamic therapy” (2018–2020).Conclusion: There will be a dramatically increasing number of publications on ferroptosis research based on the current global trends. China has made significant progress in ferroptosis research, but the United States is actually dominated in this field. More focus will be placed on neurodegeneration, chemotherapy, nuclear factor κB, and photodynamic therapy, which may be the next popular topics in ferroptosis research.

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Broadening horizons: the role of ferroptosis in cancer

Cited by 1,349 publications

References 183 publications

Characteristics and Biomarkers of Ferroptosis

Characteristics and Biomarkers of Ferroptosis

Construction and External Validation of a Ferroptosis-Related Gene Signature of Predictive Value for the Overall Survival in Bladder Cancer

Global Research Trends of Ferroptosis: A Rapidly Evolving Field With Enormous Potential

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