Abstract
Cellular redox homeostasis is an essential, dynamic process that ensures the balance between reducing and oxidizing reactions within cells and thus has implications across all areas of biology. Changes in levels of reactive oxygen species can disrupt redox homeostasis, leading to oxidative or reductive stress that contributes to the pathogenesis of many malignancies, including cancer. From transformation and tumor initiation to metastatic dissemination, increasing reactive oxygen species in cancer cells can paradoxically promote or suppress the tumorigenic process, depending on the extent of redox stress, its spatiotemporal characteristics and the tumor microenvironment. Here we review how redox regulation influences tumorigenesis, highlighting therapeutic opportunities enabled by redox-related alterations in cancer cells.
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Acknowledgements
We thank R. Pillai, J. P. Bossowski, M. A. Cross, W. Wu, M. Mancini and C. Wiel for critical reading of this review. T.P. is supported by National Institutes of Health (NIH) grants (R37CA222504 and R01CA227649), an American Cancer Society Research Scholar Grant (RSG-17-200-01–TBE) and the Emerald Foundation Young Investigator Award. V.I.S. is supported by the Swedish Research Council (2018-02318 and 2022-00971), the Swedish Society for Medical Research (S18-034) and the Swedish Cancer Society (20-1278). K.W. is supported by NIH training grants (T32GM136573 and T32GM136542), NIH grant (F30CA275258) and a Ruth L. Kirschstein Individual Predoctoral NRSA fellowship (F30CA275258). A.E.E.Z. is supported by the AG fund (FB20-55).
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V.I.S. consults for Pretzel Therapeutics. T.P. reports grants from Dracen Pharmaceuticals, grants from Kymera Therapeutics, grants from Bristol Myers Squibb, grants from Agios Pharmaceuticals, personal fees from Vividion Therapeutics, personal fees from Tohoku University and personal fees from Faeth Therapeutics outside the submitted work. In addition, T.P. has a patent for US-20210361603-A1 pending and a patent for US-20210085763-A1 pending. K.W. and A.E.E.Z. declare no competing interests.
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Wu, K., El Zowalaty, A.E., Sayin, V.I. et al. The pleiotropic functions of reactive oxygen species in cancer. Nat Cancer 5, 384–399 (2024). https://doi.org/10.1038/s43018-024-00738-9
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DOI: https://doi.org/10.1038/s43018-024-00738-9
