Combined PARP and WEE1 inhibition triggers anti-tumor immune response in BRCA1/2 wildtype triple-negative breast cancer
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
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.


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Last Modified: 2023-11-14 12:43:26

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