The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells

Gene Ching Chiek Koh, Soraya Boushaki, Salome Jingchen Zhao, Andrew Marcel Pregnall, Firas Sadiyah, Cherif Badja, Yasin Memari, Ilias Georgakopoulos-Soares, Serena Nik-Zainal

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Abstract

The chemotherapeutic agent CX-5461, or pidnarulex, has been fast-tracked by the United States Food and Drug Administration for early-stage clinical studies of BRCA1-, BRCA2- and PALB2-mutated cancers. It is under investigation in phase I and II trials. Here, we find that, although CX-5461 exhibits synthetic lethality in BRCA1-/BRCA2-deficient cells, it also causes extensive, nonselective, collateral mutagenesis in all three cell lines tested, to magnitudes that exceed known environmental carcinogens.

Original languageEnglish (US)
Pages (from-to)23-26
Number of pages4
JournalNature Genetics
Volume56
Issue number1
DOIs
StatePublished - Jan 2024

All Science Journal Classification (ASJC) codes

  • Genetics

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