The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells
Ching Chiek Koh, Soraya Boushaki, Salome Jingchen Zhao, Andrew M. Pregnall, Firas Sadiyah, Cherif Badja, Yasin Memari, Ilias Georgakopoulos‐Soares, Serena Nik‐Zainal
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.
Topics & Concepts
BiologyMutagenMutagenesisDrugCancer researchCarcinogenGeneticsMutationGenotypeChemotherapeutic drugsPharmacologyChemotherapyGeneDNA Repair MechanismsCRISPR and Genetic EngineeringCancer Genomics and Diagnostics