Background: PARP inhibitors have shown promising clinical results in cancer patients carrying BRCA1/2 mutations.\nTheir clinical efficacy could logically be influenced by PARP1 protein levels in patient tumors.\nMethods: We screened three cohorts of patients with ovarian cancer, totaling 313 samples, and evaluated PARP1\nprotein expression by immunohistochemistry with further validation by western blotting.\nResults: We observed that up to 60 % of tumors showed little PARP1 protein expression. In serous ovarian tumors,\ncomparing intratumoral PARP1 expression between chemo-na�¯ve and post-chemotherapy patients revealed a decrease\nin intratumoral PARP1 following chemotherapy in all three cohorts (immunohistochemistry: p < 0.001, n = 239; western\nblot: p = 0.012, n = 74). The findings were further confirmed in a selection of matched samples from the same patients\nbefore and after chemotherapy.\nConclusion: Our data suggest that patients should be screened for PARP1 expression prior to therapy with PARP\ninhibitors. Further, the observed reduction of intratumoral PARP1 post-chemotherapy suggests that treating\nchemo-na�¯ve patients with PARP inhibitors prior to the administration of chemotherapy, or concurrently, might\nincrease the responsiveness to PARP1 inhibition. Thus, a change in the timing of PARP inhibitor administration may be\nwarranted for future clinical trials.
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