title: PARP and other prospective targets for poisoning cancer cell metabolism.
abstract: Increasing evidence indicates that cancer cells rewire their metabolism during tumorigenesis. The high intracellular levels of lactate and reactive oxygen species (ROS) generated during enhanced aerobic glycolysis and mitochondrial oxidative phosphorylation respectively led to oxidative stress. The detoxification of these accumulating metabolites and the equilibrium between reduced and oxidized nicotine adenine dinucleotide (NADH and NAD(+)) are two prominent mechanisms regulating redox status and hence energy homeostasis in tumors. Targeting both processes may thus be selectively cytotoxic for cancer cells. In this context, the impact of poly(ADP-ribose) polymerase (PARP) inhibitors, a class of anticancer agents employed for the treatment of DNA repair deficient tumors, on energy homeostasis and mitochondrial respiration regulation has potential clinical implications. Here we provide an overview of the metabolic reprogramming occurring in cancer cells and discuss the translational perspectives of targeting tumor metabolism and redox balance for antineoplastic therapy.
authors.affiliation: Institut Gustave Roussy, 94805 Villejuif, France; Equipe 11, Centre de Recherche des Cordeliers, Paris 75005, France; Metabolomics Platform, Institut Gustave Roussy, 94805 Villejuif, France.
authors.forename: Judith
authors.initials: J
authors.lastname: Michels
authors.affiliation: Equipe 11, Centre de Recherche des Cordeliers, Paris 75005, France; Metabolomics Platform, Institut Gustave Roussy, 94805 Villejuif, France; Université de Paris Sud, Paris 11, 94805 Villejuif, France.
authors.forename: Florine
authors.initials: F
authors.lastname: Obrist
authors.affiliation: Equipe 11, Centre de Recherche des Cordeliers, Paris 75005, France; Metabolomics Platform, Institut Gustave Roussy, 94805 Villejuif, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Castedo
authors.affiliation: Regina Elena National Cancer Institute, 00144 Roma, Italy. Electronic address: iliovit@gmail.com.
authors.forename: Ilio
authors.initials: I
authors.lastname: Vitale
authors.affiliation: Institut Gustave Roussy, 94805 Villejuif, France; Equipe 11, Centre de Recherche des Cordeliers, Paris 75005, France; Metabolomics Platform, Institut Gustave Roussy, 94805 Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris 75908, France; Université Paris Descartes, Faculty of Medicine, Paris 75005, France. Electronic address: kroemer@orange.fr.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009243:NAD / Q000502:physiology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: Autophagy; Mitochondria; NADPH; PARP-1; Sirtuin