title: PARP inhibitors in ovarian cancer: current status and future promise.
abstract: Clinical investigation of poly(ADP-ribose) polymerase (PARP) inhibitors for ovarian cancer treatment has rapidly evolved from observations of single-agent in vitro activity of these agents in BRCA-deficient cancer cells in 2005 to the initiation of multiple phase III studies in 2013. With clinical trial design and treatment of ovarian cancer increasingly based on histological and molecular characteristics, PARP inhibitors are on the horizon of becoming the first biologic agents to be used to treat ovarian cancer based upon pre-selection characteristics of the patient's cancer. PARP inhibitors are most active in ovarian cancers that have defects or aberrations in DNA repair; use of these agents has been of particular interest in high grade serous cancers (HGSC), where studies have shown that ~50% of HGSC have abnormalities of DNA repair through BRCA germline and somatic mutation, post-translational changes of BRCA, and abnormalities of other DNA repair molecules. In addition, as aberrant DNA pathways in other histological subtypes of ovarian cancer are identified, and through the combination of PARP inhibitors with other biologic agents, the pool of eligible patients who may benefit from PARP inhibitors will likely expand. Pending review by the Food and Drug Administration (FDA) and the outcome of confirmatory phase III studies, PARP inhibitors could become the first FDA-approved biologic agent for ovarian cancer and also the first new FDA-approval in ovarian cancer since carboplatin and gemcitabine were approved for platinum sensitive ovarian cancer in 2006. This review discusses the PARP inhibitors that are currently in testing for ovarian cancer treatment and the future of this class of anti-cancer agents.
authors.affiliation: Gynecologic Oncology Program, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, USA.
authors.forename: Joyce F
authors.initials: JF
authors.lastname: Liu
authors.affiliation: Gynecologic Oncology Program, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, USA.
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Konstantinopoulos
authors.affiliation: Gynecologic Oncology Program, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston, MA 02215, USA. Electronic address: ursula_matulonis@dfci.harvard.edu.
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D004260:DNA Repair; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D007191:Indazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010793:Phthalazines / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D007191:Indazoles; D007211:Indoles; D010793:Phthalazines; D010879:Piperazines; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib; C531549:rucaparib; C586365:talazoparib; C545685:niraparib; C531550:olaparib
keywords: BRCA; Ovarian cancer; PARP inhibitors