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Nat Genet ; 56(1): 23-26, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38036782

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.


Subject(s)
Mutagens , Neoplasms , Humans , Mutagens/toxicity , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Benzothiazoles/therapeutic use , Naphthyridines , Neoplasms/drug therapy
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