PARP inhibitors and epithelial ovarian cancer: Molecular mechanisms, clinical development and future prospective (Review)

Epithelial ovarian cancer (EOC) has a poor prognosis. Since the introduction of paclitaxel as antineoplastic agent >20 years ago, only a few phase III randomized trials have shown challenging data regarding different therapeutic options for facing its aggressive clinical course and granting active therapies to patients. Different studies have shown the utility of poly(ADP-ribose) polymerase (PARP) inhibitors in women with EOC with or without BRCA mutations, both germline and somatic. Three PARP inhibitors, olaparib, rucaparib and niraparib, have been recently approved by the Food and Drug Administration for clinical use in EOC patients, though with different clinical indications and profiles of toxicity, while two other molecules, veliparib and talazoparib, are still under clinical investigation. The aim of the present paper is to evaluate the current status of PARP inhibitors in terms of molecular activity, pharmacodynamic properties and clinical applications. Contents 1. Introduction 2. BRCA mutations and cancer risk 3. Molecular mechanisms of PARP enzymes 4. Biological link between PARP and angiogenesis inhibition 5. Clinical application of PARP inhibitors in BRCA mutations, mechanisms of activity and resistance 6. Clinical trials with PARP inhibitors in EOC 7. Selection of PARP inhibitors in EOC 8. Future development of PARP inhibitors in EOC