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Targeting ROS in cancer: rationale and strategies

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From Nature Reviews Drug Discovery

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Abstract

Reactive oxygen species (ROS) in biological systems are transient but essential molecules that are generated and eliminated by a complex set of delicately balanced molecular machineries. Disruption of redox homeostasis has been associated with various human diseases, especially cancer, in which increased ROS levels are thought to have a major role in tumour development and progression. As such, modulation of cellular redox status by targeting ROS and their regulatory machineries is considered a promising therapeutic strategy for cancer treatment. Recently, there has been major progress in this field, including the discovery of novel redox signalling pathways that affect the metabolism of tumour cells as well as immune cells in the tumour microenvironment, and the intriguing ROS regulation of biomolecular phase separation. Progress has also been made in exploring redox regulation in cancer stem cells, the role of ROS in determining cell fate and new anticancer agents that target ROS. This Review discusses these research developments and their implications for cancer therapy and drug discovery, as well as emerging concepts, paradoxes and future perspectives.

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Fig. 1: ROS-mediated signalling processes, crosstalk with metabolism, and impact on tumour microenvironment and immune functions.
Fig. 2: Graded dose–effect of ROS on cancer and immune cell functions.
Fig. 3: Role of ROS in phase separation.
Fig. 4: ROS stress adaptation in cancer stem cells and its role in metastasis and therapeutic resistance.
Fig. 5: Role of ROS in induction of regulated cell death.
Fig. 6: Strategies to target ROS in cancer.

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Acknowledgements

This work was supported in part by a grant from the Ministry of Science and Technology of the People’s Republic of China (2020YFA0803300). D.T. received support from Mahidol University Fundamental Fund: fiscal year 2023 by National Science Research and Innovation Fund (NSRF) of Thailand. We thank X. **a of the Sun Yat-sen University Cancer Center for helpful discussion. The authors apologize for any papers and topics that could not be included in this article due to space limitations.

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

    Christophe Glorieux, Shihua Liu & Peng Huang

  2. Institute of Nutrition, Mahidol University, Nakhon Pathom, Thailand

    Dunyaporn Trachootham

  3. Metabolic Innovation Center, Sun Yat-Sen University, Guangzhou, China

    Peng Huang

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  1. Christophe Glorieux
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  2. Shihua Liu
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All authors researched data for the article, contributed substantially to the discussion of its content, and wrote, reviewed and edited the manuscript before submission. C.G. and S.L. contributed equally to this work.

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Correspondence to Peng Huang.

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Glorieux, C., Liu, S., Trachootham, D. et al. Targeting ROS in cancer: rationale and strategies. Nat Rev Drug Discov (2024). https://doi.org/10.1038/s41573-024-00979-4

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