title: Poly ADP-ribose polymerase inhibitors: science and current clinical development.
abstract: OBJECTIVE
  Poly ADP-ribose polymerase inhibitors are a promising new area in cancer therapeutics. This review summarizes the current understanding of their mechanism of action, their state of clinical development, and possible mechanisms of resistance.
  
  
  RESULTS
  Poly ADP-ribose polymerase inhibitors were predicted to cause lethality in cells with lesions in homologous recombination, as well as to be synergistic with cytotoxic chemotherapy. Recent clinical trial results have validated both of these hypotheses. In addition, studies have begun to examine possible mechanisms of resistance.
  
  
  CONCLUSIONS
  Poly ADP-ribose polymerase inhibitors were developed with the idea of synthetic lethality in mind, a concept from classical genetics that may be a general approach to finding new targets for cancer therapy. They show activity as monotherapy in cancers with defective homologous recombination, and they may potentiate the action of conventional cytotoxic chemotherapy.
authors.affiliation: Women's Cancers Program, Medical Oncology Department, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joyce F
authors.initials: JF
authors.lastname: Liu
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Silver
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors