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Exploiting ferroptosis vulnerabilities in cancer

Abstract

Ferroptosis is a distinct lipid peroxidation-dependent form of necrotic cell death. This process has been increasingly contemplated as a new target for cancer therapy because of an intrinsic or acquired ferroptosis vulnerability in difficult-to-treat cancers and tumour microenvironments. Here we review recent advances in our understanding of the molecular mechanisms that underlie ferroptosis and highlight available tools for the modulation of ferroptosis sensitivity in cancer cells and communication with immune cells within the tumour microenvironment. We further discuss how these new insights into ferroptosis-activating pathways can become new armouries in the fight against cancer.

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Fig. 1: Overview of the main pathways that regulate ferroptosis.
Fig. 2: Crosstalk between ferroptotic cancer cells and the immune system.
Fig. 3: Perspectives for targeting ferroptosis in cancer.

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Acknowledgements

The authors would like to apologize to all those colleagues whose work has not been cited here owing to space constraints. M.C. received funding from the Deutsche Forschungsgemeinschaft (DFG) (CO 291/7-1, the Priority Program SPP 2306 (CO 291/9-1, 461385412; CO 291/10-1, 461507177) and the CRC TRR 353 (CO 291/11-1; 471011418), the German Federal Ministry of Education and Research (BMBF) FERROPATH (01EJ2205B) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. GA 884754).

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M.C. is a co-founder and shareholder of ROSCUE Therapeutics. M.C. and T.N. have filed patents for some of the compounds described herein.

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Nakamura, T., Conrad, M. Exploiting ferroptosis vulnerabilities in cancer. Nat Cell Biol (2024). https://doi.org/10.1038/s41556-024-01425-8

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