title: Epidermal growth factor receptor mutation status and rad51 determine the response of glioblastoma to multimodality therapy with cetuximab, temozolomide, and radiation.
abstract: OBJECTIVE
  EGFR amplification and mutation (i.e., EGFRvIII) are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolomide (TMZ), and radiation therapy (RT).
  
  
  METHODS
  In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR) and the other overexpressing EGFRvIII (U87EGFRvIII).
  
  
  RESULTS
  Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing.
  
  
  CONCLUSIONS
  The difference in sensitivity between EGFR-expressing and EGFRvIII-expressing tumors to combined modality treatment may help in the future tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant.
authors: Molecular Radiation Biology, Department of Radiation Oncology, Thomas Jefferson University Philadelphia, PA, USA.
authors: Phyllis Rachelle
authors: PR
authors: Wachsberger
authors: Richard Yaacov
authors: RY
authors: Lawrence
authors: Yi
authors: Y
authors: Liu
authors: Barbara
authors: B
authors: Rice
authors: Constantine
authors: C
authors: Daskalakis
authors: Adam P
authors: AP
authors: Dicker
keywords: EGFR; GBM; Rad51; cetuximab; radiation therapy; temozolomide
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