Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
    • CME
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CCR Focus Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Breast Cancer
      • Clinical Trials
      • Immunotherapy: Facts and Hopes
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Clinical Cancer Research
Clinical Cancer Research
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
    • CME
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • CCR Focus Archive
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Breast Cancer
      • Clinical Trials
      • Immunotherapy: Facts and Hopes
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Translational Cancer Mechanisms and Therapy

AsiDNA Is a Radiosensitizer with no Added Toxicity in Medulloblastoma Pediatric Models

Sofia Ferreira, Chloe Foray, Alberto Gatto, Magalie Larcher, Sophie Heinrich, Mihaela Lupu, Joel Mispelter, François D. Boussin, Célio Pouponnot and Marie Dutreix
Sofia Ferreira
1Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
2Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chloe Foray
1Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
2Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alberto Gatto
3Institut Curie, Paris Sciences et Lettres Research University, Centre National de la Recherche Scientifique, UMR3664, Equipe Labellisée Ligue contre le Cancer, Paris, France.
4Sorbonne Universités, Université Pierre et Marie Curie Paris 06, Centre National de la Recherche Scientifique, UMR3664, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Magalie Larcher
1Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
2Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sophie Heinrich
1Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
2Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mihaela Lupu
5Institut Curie, Research Center, PSL Research University, CNRS UMR 9187, INSERM U 1196, Orsay, Paris, France.
6Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 9187, INSERM U1196, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joel Mispelter
5Institut Curie, Research Center, PSL Research University, CNRS UMR 9187, INSERM U 1196, Orsay, Paris, France.
6Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 9187, INSERM U1196, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
François D. Boussin
7Université de Paris and Université Paris-Saclay, Inserm, LRP/iRCM/IBFJ CEA, UMR Stabilité Génétique Cellules Souches et Radiations, F-92265, Fontenay-aux-Roses, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Célio Pouponnot
1Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
2Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie Dutreix
1Institut Curie, PSL Research University, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
2Institut Curie, Université Paris-Sud, Université Paris-Saclay, CNRS UMR 3347, INSERM U1021, Orsay, Paris, France.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: marie.dutreix@curie.fr
DOI: 10.1158/1078-0432.CCR-20-1729 Published November 2020
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below.

Abstract

Purpose: Medulloblastoma is an important cause of mortality and morbidity in pediatric oncology. Here, we investigated whether the DNA repair inhibitor, AsiDNA, could help address a significant unmet clinical need in medulloblastoma care, by improving radiotherapy efficacy without increasing radiation-associated toxicity.

Experimental Design: To evaluate the brain permeability of AsiDNA upon systemic delivery, we intraperitoneally injected a fluorescence form of AsiDNA in models harboring brain tumors and in models still in development. Studies evaluated toxicity associated with combination of AsiDNA with radiation in the treatment of young developing animals at subacute levels, related to growth and development, and at chronic levels, related to brain organization and cognitive skills. Efficacy of the combination of AsiDNA with radiation was tested in two different preclinical xenografted models of high-risk medulloblastoma and in a panel of medulloblastoma cell lines from different molecular subgroups and TP53 status. Role of TP53 on the AsiDNA-mediated radiosensitization was analyzed by RNA-sequencing, DNA repair recruitment, and cell death assays.

Results: Capable of penetrating young brain tissues, AsiDNA showed no added toxicity to radiation. Combination of AsiDNA with radiotherapy improved the survival of animal models more efficiently than increasing radiation doses. Medulloblastoma radiosensitization by AsiDNA was not restricted to a specific molecular group or status of TP53. Molecular mechanisms of AsiDNA, previously observed in adult malignancies, were conserved in pediatric models and resembled dose increase when combined with irradiation.

Conclusions: Our results suggest that AsiDNA is an attractive candidate to improve radiotherapy in medulloblastoma, with no indication of additional toxicity in developing brain tissues.

Footnotes

  • Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

  • Clin Cancer Res 2020;26:5735–46

  • Received May 10, 2020.
  • Revision received July 8, 2020.
  • Accepted August 25, 2020.
  • Published first September 8, 2020.
  • ©2020 American Association for Cancer Research.
View Full Text

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top
Clinical Cancer Research: 26 (21)
November 2020
Volume 26, Issue 21
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Clinical Cancer Research article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
AsiDNA Is a Radiosensitizer with no Added Toxicity in Medulloblastoma Pediatric Models
(Your Name) has forwarded a page to you from Clinical Cancer Research
(Your Name) thought you would be interested in this article in Clinical Cancer Research.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
AsiDNA Is a Radiosensitizer with no Added Toxicity in Medulloblastoma Pediatric Models
Sofia Ferreira, Chloe Foray, Alberto Gatto, Magalie Larcher, Sophie Heinrich, Mihaela Lupu, Joel Mispelter, François D. Boussin, Célio Pouponnot and Marie Dutreix
Clin Cancer Res November 1 2020 (26) (21) 5735-5746; DOI: 10.1158/1078-0432.CCR-20-1729

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
AsiDNA Is a Radiosensitizer with no Added Toxicity in Medulloblastoma Pediatric Models
Sofia Ferreira, Chloe Foray, Alberto Gatto, Magalie Larcher, Sophie Heinrich, Mihaela Lupu, Joel Mispelter, François D. Boussin, Célio Pouponnot and Marie Dutreix
Clin Cancer Res November 1 2020 (26) (21) 5735-5746; DOI: 10.1158/1078-0432.CCR-20-1729
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Genomic and Epigenomic Profiling of FH-deficient RCC
  • Tarloxotinib Is a Hypoxia-Activated pan-HER Kinase Inhibitor
  • CEACAM7-directed CAR T-cell Therapy of Pancreatic Cancer
Show more Translational Cancer Mechanisms and Therapy
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • CCR Focus Archive
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Clinical Cancer Research

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Clinical Cancer Research
eISSN: 1557-3265
ISSN: 1078-0432

Advertisement