TY - JOUR
T1 - Broadening horizons
T2 - the role of ferroptosis in cancer
AU - Chen, Xin
AU - Kang, Rui
AU - Kroemer, Guido
AU - Tang, Daolin
N1 - Funding Information:
We thank D. Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript. G.K. is supported by the Agence National de la Recherche (ANR)–Projets blancs; ANR under the frame of the ERA-Net for Research on Rare Diseases (E-Rare-2); Association pour la recherche sur le cancer; Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix); a donation from Elior; European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); Fondation Carrefour; Fondation pour la Recherche Médicale; Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome; High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051); Inserm (HTE); Institut National du Cancer; Institut Universitaire de France; LabEx Immuno-Oncology; LeDucq Foundation; Ligue contre le Cancer (équipe labellisée); RHU Torino Lumière; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumour Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM).
Publisher Copyright:
© 2021, Springer Nature Limited.
PY - 2021/5
Y1 - 2021/5
N2 - The discovery of regulated cell death processes has enabled advances in cancer treatment. In the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been implicated in the development and therapeutic responses of various types of tumours. Experimental reagents (such as erastin and RSL3), approved drugs (for example, sorafenib, sulfasalazine, statins and artemisinin), ionizing radiation and cytokines (such as IFNγ and TGFβ1) can induce ferroptosis and suppress tumour growth. However, ferroptotic damage can trigger inflammation-associated immunosuppression in the tumour microenvironment, thus favouring tumour growth. The extent to which ferroptosis affects tumour biology is unclear, although several studies have found important correlations between mutations in cancer-relevant genes (for example, RAS and TP53), in genes encoding proteins involved in stress response pathways (such as NFE2L2 signalling, autophagy and hypoxia) and the epithelial-to-mesenchymal transition, and responses to treatments that activate ferroptosis. Herein, we present the key molecular mechanisms of ferroptosis, describe the crosstalk between ferroptosis and tumour-associated signalling pathways, and discuss the potential applications of ferroptosis in the context of systemic therapy, radiotherapy and immunotherapy.
AB - The discovery of regulated cell death processes has enabled advances in cancer treatment. In the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been implicated in the development and therapeutic responses of various types of tumours. Experimental reagents (such as erastin and RSL3), approved drugs (for example, sorafenib, sulfasalazine, statins and artemisinin), ionizing radiation and cytokines (such as IFNγ and TGFβ1) can induce ferroptosis and suppress tumour growth. However, ferroptotic damage can trigger inflammation-associated immunosuppression in the tumour microenvironment, thus favouring tumour growth. The extent to which ferroptosis affects tumour biology is unclear, although several studies have found important correlations between mutations in cancer-relevant genes (for example, RAS and TP53), in genes encoding proteins involved in stress response pathways (such as NFE2L2 signalling, autophagy and hypoxia) and the epithelial-to-mesenchymal transition, and responses to treatments that activate ferroptosis. Herein, we present the key molecular mechanisms of ferroptosis, describe the crosstalk between ferroptosis and tumour-associated signalling pathways, and discuss the potential applications of ferroptosis in the context of systemic therapy, radiotherapy and immunotherapy.
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U2 - 10.1038/s41571-020-00462-0
DO - 10.1038/s41571-020-00462-0
M3 - Review article
C2 - 33514910
AN - SCOPUS:85099477973
SN - 1759-4774
VL - 18
SP - 280
EP - 296
JO - Nature Reviews Clinical Oncology
JF - Nature Reviews Clinical Oncology
IS - 5
ER -