Widening the BRCAness therapeutic window for its synthetic lethality effects with PARP inhibitors
Abstract
This review examines the expanding role of PARP inhibitors in cancer therapy, moving beyond the traditional model of single-strand break repair inhibition and BRCA-dependent synthetic lethality. We highlight emerging evidence that PARP inhibitors induce cytotoxicity through replication-associated DNA damage, including defects in Okazaki fragment maturation and replication gap accumulation. By integrating recent mechanistic insights with findings from CRISPR-based screens, we outline how disruptions in DNA replication and repair pathways define a broader BRCAness phenotype. We further emphasize the clinical implications of these discoveries, including novel combination strategies that extend the therapeutic applicability of PARP inhibitors beyond prevailing treatment regimens.
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BibTeX
@article{fernandez2026widening,
title = {{Widening the BRCAness therapeutic window for its synthetic lethality effects with PARP inhibitors}},
author = {Anthony Fernandez and Yuvika Salman and Roxanne Castillo and Carlotta Glackin and Binghui Shen},
journal = {Communications Biology},
year = {2026},
month = nov,
doi = {10.1038/s42003-026-11257-x},
url = {https://www.nature.com/articles/s42003-026-11257-x},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Widening the BRCAness therapeutic window for its synthetic lethality effects with PARP inhibitors
AU - Anthony Fernandez
AU - Yuvika Salman
AU - Roxanne Castillo
AU - Carlotta Glackin
AU - Binghui Shen
PY - 2026
DA - 2026/11/02
JO - Communications Biology
DO - 10.1038/s42003-026-11257-x
UR - https://www.nature.com/articles/s42003-026-11257-x
AB - This review examines the expanding role of PARP inhibitors in cancer therapy, moving beyond the traditional model of single-strand break repair inhibition and BRCA-dependent synthetic lethality. We highlight emerging evidence that PARP inhibitors induce cytotoxicity through replication-associated DNA damage, including defects in Okazaki fragment maturation and replication gap accumulation. By integrating recent mechanistic insights with findings from CRISPR-based screens, we outline how disruptions in DNA replication and repair pathways define a broader BRCAness phenotype. We further emphasize the clinical implications of these discoveries, including novel combination strategies that extend the therapeutic applicability of PARP inhibitors beyond prevailing treatment regimens.
SN - 2399-3642
ER -