However, there is strong evidence that patients with metastatic, castration resistant prostate cancer who have DNA damage repair defects respond positively to targeting PARP enzymes.
These findings suggest a new therapeutic strategy for ATM-mutant CRPC patients by targeting LDHA-mediated glycolysis metabolism, which might be effective for the PARP inhibitor resistant mCRPC tumors.
Recent findings from a phase II trial suggest that combining the antiandrogen abiraterone and the PARP inhibitor olaparib significantly improves progression-free survival among patients with metastatic castration-resistant prostate cancer, regardless of their homologous recombination repair-mutation status.
A single-arm phase 2 study of the PARP inhibitor olaparib demonstrated high response rates and more favorable progression-free and overall survival for men with metastatic castration-resistant prostate cancer and DNA repair defects treated with olaparib compared with men without DNA repair defects.
Purpose To determine whether cotargeting poly (ADP-ribose) polymerase-1 plus androgen receptor is superior to androgen receptor inhibition in metastatic castration-resistant prostate cancer (mCRPC) and whether ETS fusions predict response.
Data from the phase II TOPARP-A clinical trial indicate that men with metastatic castration-resistant prostate cancer are more likely to respond to the PARP inhibitor olaparib if they have mutations in DNA damage repair genes.
Defining the EMT control by PARP-1 during prostate cancer progression is of translational significance for optimizing PARP-1 therapeutic targeting and predicting response in metastatic castration-resistant prostate cancer.