Epithelial ovarian cancer (EOC) accounts for nearly 90% of all ovarian
malignancies. The standard therapeutic strategy includes
cytoreductive surgery and neo (adjuvant)
platinum-based
chemotherapy. Relapse of advanced high grade serous
ovarian cancer (HGSOC) is related to the development of drug resistance. A defective DNA damage response is a defining hallmark of HGSOC.
Poly (ADP-ribose) polymerase (
PARP) inhibitors exploit this deficiency through synthetic lethality and have emerged as promising anticancer
therapies, especially in
breast cancer gene (BRCA1 or BRCA2) mutation carriers. Apart from inducing synthetic lethality,
PARP inhibitors have also been shown to trap PARP1 and PARP2 on
DNA, leading to PARP-
DNA complexes. This "PARP trapping" potentiates synergism between PARP inhibition and both
alkylating agents and
platinum-based
chemotherapy. However, there are remarkable differences in the ability of
PARP inhibitors to trap PARP, based on the size and structure of each separate molecule. Since monotherapy with
PARP inhibitors is unlikely to induce
cancer cell death in BRCA-proficient
tumors, the efficacy of
PARP inhibitors could be potentially optimized when combined with
DNA-damaging agents, or with molecular targeted agents that also impair mechanisms of DNA repair.
Olaparib,
rucaparib, and
niraparib have all obtained US Food and Drug Administration (FDA) and/or European Medicines Agency (EMA) approval in
ovarian cancer in different settings.
Veliparib does not yet have an approved label; nevertheless, there are currently promising results available in preclinical and early clinical settings. This comprehensive review summarizes the mechanism of action of
veliparib and provides an overview of its early and ongoing clinical investigations.