title: Stumbling blocks on the path to personalized medicine in breast cancer: the case of PARP inhibitors for BRCA1/2-associated cancers.
abstract: The popular vision for the future of oncology includes the rational design of therapies inhibiting specific targets, for which development would be less expensive and the chance of success greater because the agent, the target, and a population predicted to benefit maximally would be known from the outset. In the breast cancer arena, successful targeted therapies have entered clinical practice. Recently, patients with BRCA-associated cancers have been identified as eligible for novel investigational therapies targeting their genetic deficiency. Preclinical data, phase I results, and 2 phase II proof-of-concept studies support the continued development of PARP inhibitors, either as single agents or in combination with specific cytotoxic drugs in this setting. In this article, we provide a brief review of current developments concerning PARP inhibitors in BRCA-associated cancers and express concerns about challenges to further development.
  
  
  CONCLUSIONS
  PARP inhibitors may represent a new and promising targeted therapy for patients with BRCA1/2 -associated cancer. In this review we summarize the main challenges in the clinical development of these agents.
authors.affiliation: Breast Cancer Center, Medical Oncology Department, University Hospital Vall d'Hebron, Barcelona, Spain. jbalmana@vhebron.net
authors.forename: Judith
authors.initials: J
authors.lastname: Balmaña
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.forename: Andrew
authors.initials: A
authors.lastname: Tutt
authors.forename: Judy E
authors.initials: JE
authors.lastname: Garber
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000378:metabolism*; D024682:BRCA2 Protein / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D057285:Precision Medicine / Q000379:methods* / Q000592:standards
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases