title: An update on PARP inhibitors--moving to the adjuvant setting.
abstract: Inhibition of poly(ADP-ribose) polymerase (PARP) enzymes is a potential synthetic lethal therapeutic strategy in cancers harbouring specific DNA-repair defects, including those arising in carriers of BRCA1 or BRCA2 mutations. Since the development of first-generation PARP inhibitors more than a decade ago, numerous clinical trials have been performed to validate their safety and efficacy, bringing us to the stage at which adjuvant therapy with PARP inhibitors is now being considered as a viable treatment option for patients with breast cancer. Nevertheless, the available data do not provide clear proof that these drugs are efficacious in the setting of metastatic disease. Advancement of a therapy to the neoadjuvant and adjuvant settings without such evidence is exceptional, but seems reasonable in the case of PARP inhibitors because the target population that might benefit from this class of drugs is small and well defined. This Review describes the evolution of PARP inhibitors from bench to bedside, and provides an up-to-date description of the key published or otherwise reported clinical trials of these agents. The specific considerations and challenges that might be encountered when implementing these compounds in the adjuvant treatment of breast cancer in the clinic are also highlighted.
authors.affiliation: BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 125, B-1000 Brussels, Belgium.
authors.forename: Amir
authors.initials: A
authors.lastname: Sonnenblick
authors.affiliation: BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 125, B-1000 Brussels, Belgium.
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
authors.affiliation: BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 125, B-1000 Brussels, Belgium.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Azim
authors.affiliation: BrEAST Data Centre, Department of Medicine, Institut Jules Bordet, Université Libre de Bruxelles, Boulevard de Waterloo 125, B-1000 Brussels, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001549:Benzamides / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000627:therapeutic use; D053903:DNA Breaks, Double-Stranded; D053904:DNA Breaks, Single-Stranded; D004260:DNA Repair / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D010793:Phthalazines / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000093542:Gemcitabine
chemical_list: D000277:Adjuvants, Pharmaceutic; D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D001549:Benzamides; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D003841:Deoxycytidine; C090712:iniparib; D016190:Carboplatin; C531550:olaparib; D000093542:Gemcitabine