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

Teo, ZL; O&#39;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

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;
Details: Publication Year 2023-08-15,Volume 9,Issue #1,Page 68
Journal Title: NPJ Breast Cancer
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: NPG
Research Division(s): Cancer Biology And Stem Cells
PubMed ID: 37582853
Publisher's Version: https://doi.org/10.1038/s41523-023-00568-5
Open Access at Publisher's Site: https://doi.org/0.1038/s41523-023-00568-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: s41523-023-00568-5.pdf - (1.48MB, application/pdf)

Creation Date: 2023-08-28 09:37:21

Last Modified: 2023-08-28 09:54:31