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CRISPR Screens Identify POLB as a Synthetic Lethal Enhancer of PARP Inhibition Exclusively in BRCA-Mutated Tumors

6 May 2025

Abstract excerpt

PARP inhibitors (PARPi) are an approved class of anticancer therapeutics that inhibit the activities of PARP1/2 and produce synthetic lethality in BRCA1/2-mutated cancers because of the absence of a functional homologous recombination-dependent DNA repair pathway. Although PARPis have led to successful clinical outcomes, two thirds of patients develop acquired resistance, limiting long-term utility as maintenance...

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PMID: 40326293
DOI: 10.1158/1535-7163.mct-24-0822

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