The efficacy and toxicity of ATM inhibition in glioblastoma initiating cells-driven tumor models

Guido Frosina, Daniela Marubbi, Diana Marcello, Donatella Vecchio, Antonio Daga

Research output: Contribution to journalReview articlepeer-review

Abstract

The Ataxia Telangiectasia Mutated (ATM)-mediated DNA damage response (DDR)is a major mechanism of resistance of glioblastoma (GB)- initiating cells (GICs)to radiotherapy. The closely related Ataxia Telangiectasia and Rad3-related protein (ATR)is also involved in tumor resistance to radio- and chemotherapy. It has been shown that pharmacological inhibition of ATM protein may overcome the DDR-mediated resistance in GICs and significantly radiosensitize GIC-driven GB. Albeit not essential for life as shown by the decade-long lifespan of AT patients, the ATM protein may be involved in a number of important functions other than the response to DNA damage. We discuss our current knowledge about the toxicity of pharmacologic inhibition of ATM and ATR proteins.

Original languageEnglish
Pages (from-to)214-222
Number of pages9
JournalCritical Reviews in Oncology/Hematology
Volume138
DOIs
Publication statusPublished - Jun 1 2019

Keywords

  • Animal models
  • Ataxia telangiectasia mutated
  • Glioma initiating cells
  • High grade glioma
  • Side effects

ASJC Scopus subject areas

  • Hematology
  • Oncology

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