Combined PARP and WEE1 inhibition triggers anti-tumor immune response in BRCA1/2 wildtype triple-negative breast cancer
- Author(s)
- Teo, ZL; O'Connor, MJ; Versaci, S; Clarke, KA; Brown, ER; Percy, LW; Kuykhoven, K; Mintoff, CP; Savas, P; Virassamy, B; Luen, SJ; Byrne, A; Sant, S; Lindeman, GJ; Darcy, PK; Loi, S;
- Journal Title
- NPJ Breast Cancer
- Publication Type
- Research article
- Abstract
- Novel therapeutic strategies that can effectively combine with immunotherapies are needed in the treatment of triple-negative breast cancer (TNBC). We demonstrate that combined PARP and WEE1 inhibition are synergistic in controlling tumour growth in BRCA1/2 wild-type TNBC preclinical models. The PARP inhibitor (PARPi) olaparib combined with the WEE1 inhibitor (WEE1i) adavosertib triggered increases in anti-tumour immune responses, including STING pathway activation. Combinations with a STING agonist resulted in further improved durable tumour regression and significant improvements in survival outcomes in murine tumour models of BRCA1/2 wild-type TNBC. In addition, we have identified baseline tumour-infiltrating lymphocyte (TIL) levels as a potential predictive biomarker of response to PARPi, WEE1i and immunotherapies in BRCA1/2 wild-type TNBC.
- Publisher
- Springer Nature
- Department(s)
- Laboratory Research; Medical Oncology
- PubMed ID
- 37582853
- Publisher's Version
- https://doi.org/10.1038/s41523-023-00568-5
- Open Access at Publisher's Site
https://doi.org/10.1038/s41523-023-00568-5- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-11-14 12:41:59
Last Modified: 2025-01-17 02:06:37