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

doi:10.1038/s41588-023-01602-9

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

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

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 language	English (US)
Pages (from-to)	23-26
Number of pages	4
Journal	Nature Genetics
Volume	56
Issue number	1
DOIs	https://doi.org/10.1038/s41588-023-01602-9
State	Published - Jan 2024

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SDG 3 Good Health and Well-being

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Genetics

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10.1038/s41588-023-01602-9

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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.",

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AU - Koh, Gene Ching Chiek

AU - Boushaki, Soraya

AU - Zhao, Salome Jingchen

AU - Pregnall, Andrew Marcel

AU - Sadiyah, Firas

AU - Badja, Cherif

AU - Memari, Yasin

AU - Georgakopoulos-Soares, Ilias

AU - Nik-Zainal, Serena

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AB - 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.

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

Abstract

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