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Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry
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Cell Cycle-specific Measurement of γH2AX and Apoptosis After Genotoxic Stress by Flow Cytometry

Published on: September 1, 2019

DNA damage response and growth factor signaling pathways in gliomagenesis and therapeutic resistance

Massimo Squatrito1, Eric C Holland

  • 1Department of Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. squatrim@mskcc.org

Cancer Research
|September 16, 2011
PubMed

Insights

Glioblastoma multiforme (GBM) therapy resistance stems from DNA damage response (DDR) pathway alterations. Targeting these DDR pathways offers new strategies to improve glioblastoma treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Glioblastoma multiforme (GBM) exhibits a poor prognosis due to limited therapeutic response.
  • The DNA damage response (DDR) pathway significantly influences tumor development and treatment efficacy.

Purpose of the Study:

  • To review findings linking GBM-driving genetic alterations to therapy resistance.
  • To explore therapeutic strategies targeting GBM genetic alterations for improved treatment response.

Main Methods:

  • Literature review focusing on the role of DDR pathways in GBM.
  • Analysis of genetic alterations in GBM (e.g., EGFR amplification, PTEN inactivation) and their impact on DNA repair.
  • Examination of therapeutic approaches to overcome or exploit these alterations.

Main Results:

  • Genetic alterations in GBM, such as EGFR amplification and PTEN inactivation, modulate DNA repair capacity.
  • These alterations contribute to the inherent resistance of GBM to DNA-damaging therapies like radiation and chemotherapy.
  • The pathways driving GBM formation are implicated in therapy resistance.

Conclusions:

  • Understanding the interplay between GBM genetics and DDR is crucial for improving treatment outcomes.
  • Therapeutic strategies aimed at overcoming or utilizing GBM-specific genetic alterations hold promise for enhancing patient response to DNA-damaging agents.

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