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

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.

• Authors: Guido Frosina, Daniela Marubbi, Diana Marcello, Donatella Vecchio, Antonio Daga
• Journal: Critical reviews in oncology/hematology (Crit Rev Oncol Hematol) Vol. 138 Pg. 214-222 (Jun 2019) ISSN: 1879-0461 [Electronic] Netherlands
• PMID: 31092378 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Radiation-Sensitizing Agents
• ATM protein, human
• ATR protein, human
• Ataxia Telangiectasia Mutated Proteins

Topics

• Adult
• Animals
• Ataxia Telangiectasia Mutated Proteins (antagonists & inhibitors)
• Brain Neoplasms (pathology)
• DNA Damage (drug effects)
• Glioblastoma (pathology)
• Humans
• Neoplastic Stem Cells (drug effects)
• Radiation Tolerance (drug effects)
• Radiation-Sensitizing Agents (pharmacology)