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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Koh et al. (2023) studied this question.
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