title: Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma.
abstract: BACKGROUND
  Glioblastoma (GBM) is the most frequent and aggressive type of adult brain tumor. Most GBMs express telomerase; a high level of intra-tumoral telomerase activity (TA) is predictive of poor prognosis. Thus, telomerase inhibitors are promising options to treat GBM. These inhibitors increase the response to radiotherapy (RT), in vitro as well as in vivo. Since typical treatments for GBM include RT, our objective was to evaluate the efficiency of Imetelstat (TA inhibitor) combined with RT.
  
  
  RESULTS
  We used a murine orthotopic model of human GBM (N = 8 to11 mice per group) and μMRI imaging to evaluate the efficacy of Imetelstat (delivered by intra-peritoneal injection) alone and combined with RT. Using a clinically established protocol, we demonstrated that Imetelstat significantly: (i) inhibited the TA in the very center of the tumor, (ii) reduced tumor volume as a proportion of TA inhibition, and (iii) increased the response to RT, in terms of tumor volume regression and survival increase.
  
  
  CONCLUSIONS
  Imetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM.
authors.affiliation: EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France. sylvain.ferrandon@hotmail.fr.|Université Claude Bernard Lyon 1, Lyon, France. sylvain.ferrandon@hotmail.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ferrandon
authors.affiliation: Team « neuro-oncology and neuro-inflammation », Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, Laennec Medicine Faculty, Lyon, France. c.malleval@laposte.net.
authors.forename: Céline
authors.initials: C
authors.lastname: Malleval
authors.affiliation: EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France. badia.elhamdani@hotmail.fr.|Hospices Civils de Lyon, South Lyon Hospital, Pierre Bénite, France. badia.elhamdani@hotmail.fr.
authors.forename: Badia
authors.initials: B
authors.lastname: El Hamdani
authors.affiliation: EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France. priscillia.montagne@univ-lyon1.fr.|Université Claude Bernard Lyon 1, Lyon, France. priscillia.montagne@univ-lyon1.fr.
authors.forename: Priscillia
authors.initials: P
authors.lastname: Battiston-Montagne
authors.affiliation: CERMEP-imagerie du vivant, Groupement Hospitalier Est, Bron, France. radu.bolbos@cermep.fr.
authors.forename: Radu
authors.initials: R
authors.lastname: Bolbos
authors.affiliation: CERMEP-imagerie du vivant, Groupement Hospitalier Est, Bron, France. langlois@cermep.fr.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Langlois
authors.affiliation: UMS 3444 gerland CNRS P.B.E.S - Ecole Normale Supérieure Lyon, Lyon, France. patrick.manas@ens-lyon.fr.
authors.forename: Patrick
authors.initials: P
authors.lastname: Manas
authors.affiliation: Geron Corporation, 149 Commonweath Drive, Menlo, Park, CA, 94025, USA. sgryaznov@aurasense.com.
authors.forename: Sergei M
authors.initials: SM
authors.lastname: Gryaznov
authors.affiliation: EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France. gersende.alphonse@univ-lyon1.fr.|Hospices Civils de Lyon, South Lyon Hospital, Pierre Bénite, France. gersende.alphonse@univ-lyon1.fr.
authors.forename: Gersende
authors.initials: G
authors.lastname: Alphonse
authors.affiliation: Université Claude Bernard Lyon 1, Lyon, France. jerome.honnorat@chu-lyon.fr.|Team « neuro-oncology and neuro-inflammation », Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, Laennec Medicine Faculty, Lyon, France. jerome.honnorat@chu-lyon.fr.|Department of neuro-oncology, Hospices civils de Lyon, Bron, France. jerome.honnorat@chu-lyon.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.affiliation: EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France. claire.rodriguez-lafrasse@univ-lyon1.fr.|Université Claude Bernard Lyon 1, Lyon, France. claire.rodriguez-lafrasse@univ-lyon1.fr.|Biochemistry Department, Transfer and Molecular Oncology Unit, South Lyon Hospital, Hospices Civils de Lyon, Pierre Bénite, France. claire.rodriguez-lafrasse@univ-lyon1.fr.
authors.forename: Claire
authors.initials: C
authors.lastname: Rodriguez-Lafrasse
authors.affiliation: EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France. delphine.poncet@univ-lyon1.fr.|Université Claude Bernard Lyon 1, Lyon, France. delphine.poncet@univ-lyon1.fr.|Biochemistry Department, Transfer and Molecular Oncology Unit, South Lyon Hospital, Hospices Civils de Lyon, Pierre Bénite, France. delphine.poncet@univ-lyon1.fr.
authors.forename: Delphine
authors.initials: D
authors.lastname: Poncet
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D004195:Disease Models, Animal; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009841:Oligonucleotides; D011836:Radiation Tolerance / Q000187:drug effects*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D009841:Oligonucleotides; D009536:Niacinamide; D019098:Telomerase; C519562:imetelstat