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.
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.
PARP1 plays a crucial role in multiple biological processes and PARP1 activation contributes to the development of various inflammatory and malignant disorders, including lung inflammatory disorders, cardiovascular disease, ovarian cancer, breast cancer, and diabetes.
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.
Indeed, three PARP1 inhibitors (Olaparib, Rucaparib, and Niraparib) have recently been approved by the Food and Drug Administration for the treatment of ovarian cancer.
Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies.
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 have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful.
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.