biostudies-literatureWang LBreast Cancer Research FoundationNational Cancer InstituteNCI NIH HHSNational Cancer Institute, United StatesBasser Center27https://www.ebi.ac.uk/biostudies/studies/S-EPMC12920871biostudies-literatureUnknown12(1)We utilized the K14-Cre Brca1^f/fTp53^f/f mouse model to investigate whether a pulse of PARP inhibitor (PARPi) ± an AKT inhibitor (AKTi) can prevent Brca1-related breast cancer. PARPi alone did not intercept or prevent tumor development. PARPi+AKTi intercepted tumors but did not prevent new tumors. These data confirm the efficacy of a PARPi and an inhibitor of PI3K signaling in treating BRCA1/2-related tumors, but this combination is not sufficient to prevent carcinogenesis.NPJ breast cancerSimultaneous inhibition of PARP/AKT to intercept nascent BRCA1/2<sup>mut</sup> breast tumors.PMC1292087125-177R21CA267088R56CA284564R01CA226776Li XLiu ZWulf GMSardella BRHeng YJWang LAronson EKfalseSimultaneous inhibition of PARP/AKT to intercept nascent BRCA1/2<sup>mut</sup> breast tumors.We utilized the K14-Cre Brca1^f/fTp53^f/f mouse model to investigate whether a pulse of PARP inhibitor (PARPi) ± an AKT inhibitor (AKTi) can prevent Brca1-related breast cancer. PARPi alone did not intercept or prevent tumor development. PARPi+AKTi intercepted tumors but did not prevent new tumors. These data confirm the efficacy of a PARPi and an inhibitor of PI3K signaling in treating BRCA1/2-related tumors, but this combination is not sufficient to prevent carcinogenesis.2026-01-01T00:00:00Z2026 Jan2026-07-16T12:59:14.898Z2026-07-09T10:56:58.806ZS-EPMC129208714154535410.1038/s41523-026-00892-6