Inhibitors of nuclear poly(ADP-ribose) polymerase (PARP) enzymes (e.g., PARP-1) have improved clinical outcomes in ovarian cancer, especially in patients with BRCA1/2 gene mutations or additional homologous recombination (HR) DNA repair pathway deficiencies.
Additionally, 3 new PARP inhibitors (olaparib, rucaparib, niraparib) have been approved for use in ovarian cancer, with different indications as maintenance therapy or treatment of recurrence.
PARP inhibitors (PARPi) represent a major advance in the treatment of ovarian cancer associated with defects in homologous recombination DNA repair (HRR), primarily due to mutations in BRCA genes.
PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful.
Several PARP inhibitors, which are oral drugs and generally well tolerated, have now received FDA approval for various ovarian cancer and breast cancer indications.
Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies.
Here we review the current therapeutic settings combining anti-angiogenesis inhibitors with chemotherapy, PARP inhibitors or immune checkpoint blockers, focusing on ovarian cancer as tumor model.
The single agent activity of PARP inhibitors (PARPi) in germline BRCA mutated (gBRCAm) breast and ovarian cancer suggests untapped potential for this new class of drug in breast cancer.
PARP inhibitors, such as Olaparib, have advanced the treatment of ovarian cancer by providing patients with an effective and molecularly-targeted maintenance therapy.
This study provides mechanistic rationales for combining CNDAC with PARP inhibitors, platinum compounds and taxanes in ovarian cancer lacking BRCA1/2 function.
Originally presumed to inhibit DNA repair, PARP inhibitors that have recently been approved by the FDA for the treatment of advanced ovarian cancer also act as DNA damaging agents by inducing PARP-DNA complexes.