Talazoparib enhances resection at DSBs and renders HR-proficient cancer cells susceptible to Polθ inhibition
We propose that talazoparib promotes low-dose, CtIP/MRE11-dependent resection and increases the reliance of irradiated HR-proficient cancer cells, on Polθ-mediated alt-EJ. The combination of Polθ inhibitors with talazoparib suppresses this option and causes further radiosensitization. The results suggest that Polθ inhibition may be exploited to maximize talazoparib radiosensitization of HR-proficient tumors in the clinic.
Authors
- Razan Hessenow (ORCID: https://orcid.org/0009-0002-1488-8103)
- Xixi Lin (ORCID: https://orcid.org/0000-0002-3161-0253)
- Maja Guberina (ORCID: https://orcid.org/0000-0003-3218-0539)
- Yanjie Sun (ORCID: https://orcid.org/0000-0001-9382-4401)
- Emil Mladenov
- Martin Stuschke (ORCID: https://orcid.org/0000-0001-6836-0940)
- George Iliakis
- Aashish Soni (ORCID: https://orcid.org/0000-0001-9696-1006)
Institutions
- Essen University Hospital (DE)
- West German Heart and Vascular Center Essen (DE)
- University of Duisburg-Essen (DE)
Publication Details
- Journal
- Radiotherapy and Oncology
- Published
- 2024-08-13
- DOI
- https://doi.org/10.1016/j.radonc.2024.110475
- Citations
- 9
- Primary Topic
- PARP inhibition in cancer therapy
- Type
- article
- Field-Weighted Citation Impact
- 2.54
Funders
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Bundesministerium für Wirtschaft und Energie