Homologous Repair‐Deficient Pancreatic Cancer: Refined Targeting of DNA Damage Response is an Effective Therapeutic Strategy
Here, we demonstrate a remarkable potency of the PARPi talazoparib in HRD PDAC. Substituting olaparib, currently the only approved inhibitor in PDAC, with talazoparib in our PAD regimen enhanced its efficacy while maintaining comparable tolerability in vivo. Importantly, we show that PAD is an effective therapeutic regimen that can be extended to the most prevalent HR-defective genotypes in PDAC including ATM, BRCA1, BRCA2 and PALB2 in a preclinical setting. Collectively, these data provide a strong rationale to implement the refined regimen, talazoparib-based PAD, as a therapeutic concept tailored for HRD PDAC patients.
Authors
- Christopher J. Halbrook (ORCID: https://orcid.org/0000-0002-3376-3114)
- Élodie Roger (ORCID: https://orcid.org/0000-0002-4930-6292)
- Lukas Perkhofer
- Jessica Lindenmayer (ORCID: https://orcid.org/0009-0001-3673-5995)
- Alexander Kleger (ORCID: https://orcid.org/0000-0003-0592-5232)
- Johann Gout (ORCID: https://orcid.org/0000-0003-0522-9800)
- Thomas Seufferlein (ORCID: https://orcid.org/0000-0003-3259-0810)
- Menar Ekizce (ORCID: https://orcid.org/0000-0001-6718-8958)
- Alica K. Beutel
- S. Calderón
Institutions
- Universität Ulm (DE)
- University of California, Irvine (US)
- University of California, Irvine Medical Center (US)
- University Hospital Ulm (DE)
- Technische Hochschule Ulm (DE)
Publication Details
- Journal
- United European Gastroenterology Journal
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1002/ueg2.12773
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00