An Inducible BRCA1 Expression System with In Vivo Applicability Uncovers Activity of the Combination of ATR and PARP Inhibitors to Overcome Therapy Resistance
Our findings identify a dose-dependent, hypomorphic HRR restoration by ∆exon11 BRCA1, help explain the variable resistance observed in BRCA1-mutant pre-clinical models expressing this hypomorph, and propose ATR inhibition in combination with PARPi as a clinical strategy to counteract therapeutic resistance mediated by ∆exon11 BRCA1 hypomorphs.
Authors
- Anna D. Staniszewska (ORCID: https://orcid.org/0000-0003-1328-1959)
- Elsa Irving (ORCID: https://orcid.org/0000-0002-4103-4210)
- Alaide Morcavallo
- Jennifer I. Moss (ORCID: https://orcid.org/0000-0003-0923-229X)
- Paul W.G. Wijnhoven (ORCID: https://orcid.org/0000-0002-5489-3006)
- Josep V. Forment (ORCID: https://orcid.org/0000-0002-7797-2583)
- Jekaterina Vohhodina-Tretjakova
- Anna Louise Beckett
- Michael P. Jacques
- Rachel S. Evans
Institutions
- AstraZeneca (United Kingdom) (GB)
Publication Details
- Journal
- Cancers
- Published
- 2026-01-20
- DOI
- https://doi.org/10.3390/cancers18020309
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- AstraZeneca
- Home Office