title: Predictive biomarkers for cancer therapy with PARP inhibitors.
abstract: Poly(ADP-ribose) polymerase (PARP) inhibitors have raised high expectations for the treatment of multiple malignancies. PARP inhibitors, which can be used as monotherapies or in combination with DNA-damaging agents, are particularly efficient against tumors with defects in DNA repair mechanisms, in particular the homologous recombination pathway, for instance due to BRCA mutations. Thus, deficient DNA repair provides a framework for the success of PARP inhibitors in medical oncology. Here, we review encouraging results obtained in recent clinical trials investigating the safety and efficacy of PARP inhibitors as anticancer agents. We discuss emerging mechanisms of regulation of homologous recombination and how inhibition of DNA repair might be used in cancer therapy. We surmise that the identification of patients that are likely to benefit from PARP inhibition will improve the clinical use of PARP inhibitors in a defined target population. Thus, we will place special emphasis on biomarker discovery.
authors.affiliation: 1] INSERM, U848, Villejuif, France [2] Institut Gustave Roussy, Villejuif, France [3] Université de Paris Sud, Villejuif, France.
authors.forename: J
authors.initials: J
authors.lastname: Michels
authors.affiliation: 1] Regina Elena National Cancer Institute, Roma, Italy [2] National Institute of Health, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Vitale
authors.affiliation: 1] Institut Gustave Roussy, Villejuif, France [2] Université de Paris Sud, Villejuif, France [3] CNRS UMR8200, Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: Saparbaev
authors.affiliation: 1] INSERM, U848, Villejuif, France [2] Institut Gustave Roussy, Villejuif, France [3] Université de Paris Sud, Villejuif, France.
authors.forename: M
authors.initials: M
authors.lastname: Castedo
authors.affiliation: 1] INSERM, U848, Villejuif, France [2] Institut Gustave Roussy, Villejuif, France [3] Université de Paris Sud, Villejuif, France [4] Metabolomics Platform, Institut Gustave Roussy, Villejuif, France [5] Centre de Recherche des Cordeliers, Paris, France [6] Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France [7] Faculty of Medicine, Université Paris Descartes, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002986:Clinical Trials as Topic; D004260:DNA Repair; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018579:Patient Selection; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1