Role of the Epidermal Growth Factor Receptor Variant (EGFRvIII) in Radiation Response of Human Breast Cancer Cells
Abstract
There is increasing evidence that the epidermal growth factor receptor (EGFR) family plays an important role in radioresistance of human breast cancer. Over-' expression of HER2 is associated with local recurrence of breast cancer after radiotherapy EGFR activation is associated with increased radioresistance vitro 2 3, and EGFR over-expression is associated with radioresistance in clinical tumor specimens. Kinase inhibitors or antibodies that perturb EGFR or HER2 signaling show promise as radio sensitizing agents both in pre-clinical and clinical studies (reviewed in 6 in gliomas, rearrangements of the EGFR gene were identified, including a commonly occurring rearrangement that results in loss of exons of the extracellular domain. This variant, EGERvIII, constitutively activates signal transduction pathways associated with proliferation and survival, and may perturb the normal interactions of the endogenous EGFR family members 8,9 EGFkvIII has been reported to be expressed in a large percentage of human breast cancers and to play an important prognostic role 10 Expression of EGFRvIII confers resistance to chemotherapeutic agents in gliomas via modulation of the apoptotic pathway, and the downstream signal transduction pathways constitutively activated in some EGFRvIll-expressing cells, Pi-3-kinase and MAPK, have been implicated in radioresistance 5,11 Thus, there is a distinct possibility that EGFRvllI may mediate radioresistance or affect activation of other EGFR family members thought to be involved in radioresistance. If so, there is potential for improving radiation response by using EGFRvIII inhibitors, which are currently in advanced stages of development for clinical use, as radiosensizing agents that would have a high specificity for tumor as opposed to normal tissues.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2002
- Accession Number
- ADB285668
Entities
People
- Carolyn I. Sartor
Organizations
- University of North Carolina at Chapel Hill