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Related Experiment Videos

Second messenger systems in human gliomas.

Roger E McLendon1, Kristi Turner, Kathryn Perkinson

  • 1Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. roger.mclendon@duke.edu

Archives of Pathology & Laboratory Medicine
|October 10, 2007
PubMed
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Identifying EGFRvIII and activated downstream targets like phospho-Akt may predict glioblastoma treatment response. Pathologists can play a role in assessing these markers for targeted EGFR kinase inhibitor therapies.

Area of Science:

  • Neuro-oncology
  • Molecular Pathology
  • Cancer Therapeutics

Background:

  • Glioblastoma (WHO grade IV) has poor prognosis (<20% 2-year survival) despite advanced treatments.
  • Epidermal growth factor receptor (EGFR) hyperexpression is common but not predictive of survival.
  • Targeting downstream signaling pathways of EGFR shows therapeutic promise.

Purpose of the Study:

  • To understand the functional significance of EGFR downstream pathways.
  • To define the pathologist's role in assessing protein activation for targeted therapies.
  • To review literature on histologic assays used in clinical trials for these drugs.

Main Methods:

  • Comprehensive literature review.
  • Analysis of primary pathology archival material from Duke University.

Related Experiment Videos

  • Evaluation of histologic assays for downstream messenger proteins.

    • Main Results:

    • EGFR variant EGFRvIII identification is potentially useful.
    • Measuring activated phospho-Akt, phospho-S6, and phospho-MAPK may predict sensitivity to EGFR kinase inhibitors.
    • No prognostic significance found for these markers independent of histologic grade.

    Conclusions:

    • EGFRvIII and activated downstream markers (phospho-Akt, phospho-S6, phospho-MAPK) may predict response to EGFR kinase inhibitors.
    • Pathologic assessment of these markers is crucial for guiding brain tumor therapy.
    • Further research is needed to establish prognostic significance independent of tumor grade.