Simultaneous inhibition of PARP/AKT to intercept nascent BRCA1/2mut breast tumors.

We utilized the K14-Cre Brca1f/fTp53f/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.