TY - JOUR
T1 - The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells
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
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2024/1
Y1 - 2024/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85178189316&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85178189316&partnerID=8YFLogxK
U2 - 10.1038/s41588-023-01602-9
DO - 10.1038/s41588-023-01602-9
M3 - Article
C2 - 38036782
AN - SCOPUS:85178189316
SN - 1061-4036
VL - 56
SP - 23
EP - 26
JO - Nature Genetics
JF - Nature Genetics
IS - 1
ER -