CX-5461 (also known as pidnarulex), currently in phase 1/2 trials, induces selective killing of homologous-recombination-deficient or BRCA1- or BRCA2-mutated tumors in preclinical models. New work confirms these findings but shows it to be a remarkably potent mutagen that induces extensive genetic changes in cultured human cells with or without BRCA1/2 mutations, raising substantial safety issues.
This is a preview of subscription content, log in via an institution to check access.
References
Fugger, K. et al. Trends Cancer 7, 1102–1118 (2021).
Chapman, J. R. et al. Mol. Cell 47, 497–510 (2012).
Gourley, C. et al. J. Clin. Oncol. 37, 2257–2269 (2019).
Pilie, P. G. et al. Clin. Cancer Res. 25, 3759–3771 (2019).
Zatreanu, D. et al. Nat. Commun. 12, 3636 (2021).
Drygin, D. et al. Cancer Res. 71, 1418–30 (2011).
Haddach, M. et al. ACS Med. Chem. Lett. 3, 602–6 (2012).
Mars, J. C. et al. NAR Cancer 2, zcaa032 (2020).
Xu, H. et al. Nat. Commun. 8, 14432 (2017).
Zimmer, J. et al. Mol. Cell 61, 449–460 (2016).
Hilton, J. et al. Nat. Commun. 13, 3607 (2022).
Khot, A. et al. Cancer Discov. 9, 1036–1049 (2019).
Koh, G. C. C. et al. Nat. Genet. https://doi.org/10.1038/s41588-023-01602-9 (2023).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
S.J.B. is a co-founder, vice-president of science strategy and a shareholder of Artios Pharma.
Rights and permissions
About this article
Cite this article
Boulton, S.J. Extraordinary collateral mutagenesis induced by CX-5461. Nat Genet 56, 12–13 (2024). https://doi.org/10.1038/s41588-023-01611-8
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41588-023-01611-8
- Springer Nature America, Inc.