DNA-repair-driven cell death compels us to rethink cancer therapies

. 2025 Aug 1.

doi: 10.1038/s41580-025-00879-4. Online ahead of print.

Radoslaw Szmyd^{1

2}, Harriet E Gee^{3

4

5}, Anthony J Cesare⁶

Affiliations

¹ Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.
² Radiation Oncology Network, Western Sydney Local Health District, Sydney, New South Wales, Australia.
³ Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia. harriet.gee@sydney.edu.au.
⁴ Radiation Oncology Network, Western Sydney Local Health District, Sydney, New South Wales, Australia. harriet.gee@sydney.edu.au.
⁵ Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia. harriet.gee@sydney.edu.au.
⁶ Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia. tcesare@cmri.org.au.

Radoslaw Szmyd et al. Nat Rev Mol Cell Biol. 2025.

. 2025 Aug 1.

doi: 10.1038/s41580-025-00879-4. Online ahead of print.

Radoslaw Szmyd^{1

2}, Harriet E Gee^{3

4

5}, Anthony J Cesare⁶

¹ Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia.
² Radiation Oncology Network, Western Sydney Local Health District, Sydney, New South Wales, Australia.
³ Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia. harriet.gee@sydney.edu.au.
⁴ Radiation Oncology Network, Western Sydney Local Health District, Sydney, New South Wales, Australia. harriet.gee@sydney.edu.au.
⁵ Westmead Clinical School, University of Sydney, Sydney, New South Wales, Australia. harriet.gee@sydney.edu.au.
⁶ Genome Integrity Unit, Children's Medical Research Institute, University of Sydney, Sydney, New South Wales, Australia. tcesare@cmri.org.au.

No abstract available

Conflict of interest statement

Competing interests: The authors declare no competing interests.

1. Boon, N. J. et al. DNA damage induces p53-independent apoptosis through ribosome stalling. Science 384, 785–792 (2024). - PubMed
1. Ogawa, A. et al. SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis. Mol. Cell 85, 894–912.e810 (2025). - PubMed
1. Szmyd, R. et al. Homologous recombination promotes non-immunogenic mitotic cell death upon DNA damage. Nat. Cell Biol. 27, 59–72 (2025). - PubMed - PMC
1. Scully, R., Panday, A., Elango, R. & Willis, N. A. DNA double-strand break repair-pathway choice in somatic mammalian cells. Nat. Rev. Mol. Cell Biol. 20, 698–714 (2019). - PubMed - PMC
1. Daum, J. R. et al. Cohesion fatigue induces chromatid separation in cells delayed at metaphase. Curr. Biol. 21, 1018–1024 (2011). - PubMed - PMC