CldU sensitizes <i>BRCA2</i> reverse-mutated cells to PARP inhibitors.

ABSTRACT: PARP inhibitors are widely used class of drugs for the treatment of homologous recombination deficient cancers, including BRCA mutated ones. These drugs led to substantial improvement in survival, particularly for patients with BRCA mutated tumors. However, many patients eventually develop resistance to PARP inhibitors, mainly due to BRCA reversion mutations. Overcoming resistance to PARP inhibitors is an unmet medical need. Recently, it has been shown that BRCA-deficient cells are hypersensitive to the thymidine analogue 5-chloro-2'-deoxyuridine (CldU), either alone or in combination with PARP inhibitors. In this study, we show, across multiple BRCA2 mutated cell lines, that CldU sensitizes PARP inhibitor-resistant cells to PARP inhibitors. This s

SUBMITTER: Zouggari N 

PROVIDER: S-EPMC12672267 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature