Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma

Molecular Cancer

Short Communication

Radu Bolbos¹  Jean-Baptiste Langlois¹  Badia El Hamdani²  Gersende Alphonse²  Priscillia Battiston-Montagne³  Sylvain Ferrandon³  Claire Rodriguez-Lafrasse⁴  Delphine Poncet⁴  Sergei M Gryaznov⁵  Céline Malleval⁶  Patrick Manas⁷  Jérôme Honnorat⁸ 

[1] CERMEP-imagerie du vivant, Groupement Hospitalier Est, Bron, France;EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France;Hospices Civils de Lyon, South Lyon Hospital, Pierre Bénite, France;EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France;Université Claude Bernard Lyon 1, Lyon, France;EMR3738, Cellular and Molecular Radiobiology Laboratory, South Lyon Charles Mérieux Medicine Faculty, Oullins, France;Université Claude Bernard Lyon 1, Lyon, France;Biochemistry Department, Transfer and Molecular Oncology Unit, South Lyon Hospital, Hospices Civils de Lyon, Pierre Bénite, France;Geron Corporation, 149 Commonweath Drive, Menlo, 94025, Park, CA, USA;Team « neuro-oncology and neuro-inflammation », Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, Laennec Medicine Faculty, Lyon, France;UMS 3444 gerland CNRS P.B.E.S - Ecole Normale Supérieure Lyon, Lyon, France;Université Claude Bernard Lyon 1, Lyon, France;Team « neuro-oncology and neuro-inflammation », Lyon Neuroscience Research Center, INSERM U1028/CNRS UMR 5292, Laennec Medicine Faculty, Lyon, France;Department of neuro-oncology, Hospices civils de Lyon, Bron, France;

关键词: Telomerase;    Glioma;    Irradiation;    Orthotopic;    GRN163L;    Imetelstat;    In vivo;   

DOI  :  10.1186/s12943-015-0376-3

 received in 2015-01-29, accepted in 2015-05-01,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundGlioblastoma (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.FindingsWe 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.ConclusionsImetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM.

【 授权许可】

Unknown   
© Ferrandon et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.