The role of PARP inhibitors in ovarian cancer: therapeutic mechanisms and clinical data

Ovarian cancer is the most lethal gynecologic cancer with a high rate of recurrence. Poly(ADP-ribose) polymerase inhibitors (PARPis) are the most active therapeutic options available for patients with recurrent epithelial ovarian cancer. The treatment is based on the mechanisms of synthetic lethality and PARP trapping, especially in cancer patients with deficiencies associated with homologous recombination (HR) including cancer with BRCA mutations. The treatment is associated with high survival rates. Our review highlights the role of BRCA 1/2 mutations in tumorigenesis. We further discussed the recent clinical data of PARPis including olaparib, niraparib and rucaparib in ovarian cancer. However, resistance to PARPis is an emerging problem, and several resistance mechanisms are significantly associated with alternating drug availability, affecting the PARylation enzyme, restoring HR or replication fork stability. PARPis represent emerging and interesting therapies for recurrent epithelial ovarian cancer.

BRCA mutation; PARP inhibitor; Homologous recombination; Synthetic lethality; Ovarian cancer

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