title: Update on hepatocellular carcinoma breakthroughs: poly(ADP-ribose) polymerase inhibitors as a promising therapeutic strategy.
abstract: Hepatocellular carcinoma is the most common form of primary liver cancer which is the fifth most common cancer in men and the seventh in women and the third most common cause of cancer-related death worldwide. Only 10-20% of patients are eligible for curative treatments that result in a 5-year survival rate of 40% to 70%. Therefore, the development of novel treatment options is necessary for the majority of patients and remains a considerable challenge. Conformal radiotherapy is used in certain circumstances and preliminary data obtained from phase 1/2 trials are showing promising curative effects. There is thus an interest in identifying drugs that can be exploited to enhance radiation sensitivity that could be used in therapy and might improve clinical outcome. Small molecules inhibitors of poly(ADP-ribose) polymerases (PARP) are an example of a radio- and chemo-sensitizing drug, as well as being an efficient single agent treatment in certain genetic backgrounds. In this review, we discuss the role of PARP-1 in hepatocellular carcinoma and present the results of preclinical studies that have assessed the potential of PARP inhibition as a single treatment or combined with chemotherapy or radiotherapy for the treatment of hepatocellular carcinoma.
authors: UMR INSERM U1052 CNRS5286, CRCL, 151, cours Albert-Thomas, 69008 Lyon, France; Université Lyon-1, 69622 Villeurbanne, France; International Agency for Research on Cancer, 150, cours Albert-Thomas, 69424 Lyon cedex 03, France.
authors: Clément
authors: C
authors: Guillot
authors: Institut Curie, Centre de Recherche, Orsay, France; Inserm U612, Centre Universitaire, Orsay, France.
authors: Janet
authors: J
authors: Hall
authors: International Agency for Research on Cancer, 150, cours Albert-Thomas, 69424 Lyon cedex 03, France.
authors: Zdenko
authors: Z
authors: Herceg
authors: UMR INSERM U1052 CNRS5286, CRCL, 151, cours Albert-Thomas, 69008 Lyon, France; Université Lyon-1, 69622 Villeurbanne, France; Hospices Civils de Lyon, Service d'Hépatologie et de Gastroentérologie, Groupement Hospitalier Lyon Nord, Lyon, France.
authors: Philippe
authors: P
authors: Merle
authors: UMR INSERM U1052 CNRS5286, CRCL, 151, cours Albert-Thomas, 69008 Lyon, France; Université Lyon-1, 69622 Villeurbanne, France. Electronic address: isabelle.chemin@inserm.fr.
authors: Isabelle
authors: I
authors: Chemin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000532:radiotherapy; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011838:Radiation-Sensitizing Agents