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Reply to ‘Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies’

Nature Reviews Cancer volume 25, pages 564–565 (2025)Cite this article

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We thank Wu et al. for their comments on our Review (Peuget, S., Zhou, X. & Selivanova, G. Translating p53-based therapies for cancer into the clinic. Nat. Rev. Cancer 24, 192–215 (2024))1; they raise some interesting points that we respond to below (Wu, J., Song, H., Xiao, S. & Lu, M. Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies. Nat. Rev. Cancer https://doi.org/10.1038/s41568-025-00826-7 (2025))2.

Approximately half of all human cancers express mutants of the tumour suppressor p53, with loss of function owing to just a single amino acid residue substitution. These p53 mutants, often overexpressed, could be regarded as a loaded gun — but with a jammed trigger. As we outlined in our Review1, this makes the idea of a cancer therapy strategy aimed at restoring wild-type p53 tumour-suppressor function to mutant p53 a very attractive goal. However, despite considerable research efforts, the field has yet to produce clinical advancements based on mutant p53 restoration.

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Authors and Affiliations

  1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

    Sylvain Peuget & Galina Selivanova

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  1. Sylvain Peuget
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  2. Galina Selivanova
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Correspondence to Sylvain Peuget or Galina Selivanova.

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The authors declare no competing interests.

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PANDA (p53 and arsenic) project: www.rescuep53.net

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Peuget, S., Selivanova, G. Reply to ‘Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies’. Nat Rev Cancer 25, 564–565 (2025). https://doi.org/10.1038/s41568-025-00825-8

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