Complex oncogenic signaling networks regulate brain tumor-initiating cells and their progenies: Pivotal roles of wild-type EGFR, EGFRvIII mutant and hedgehog cascades and novel multitargeted therapies

Murielle Mimeault, Surinder K. Batra

Research output: Contribution to journalReview article

21 Scopus citations


Complex signaling cross-talks between different growth factor cascades orchestrate the primary brain cancer development. Among the frequent deregulated oncogenic pathways, the ligand-activated wild-type epidermal growth factor receptor (EGFR), constitutively activated EGFRvIII mutant and sonic hedgehog pathways have attracted much attention because of their pivotal roles in pediatric medulloblastomas and adult glioblastoma multiformes (GBM) brain tumors. The enhanced expression levels and activation of EGFR, EGFRvIII mutant and hedgehog signaling elements can provide key roles for the sustained growth, migration and local invasion of brain tumor-initiating cells (BTICs) and their progenies, resistance to current therapies and disease relapse. These tumorigenic cascades also can cooperate with Wnt/β-catenin, Notch, platelet-derived growth factor (PDGF)/PDGF receptors (PDGFRs), hepatocyte growth factor (HGF)/c-Met receptor and vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFRs) for the acquisition of a more malignant behavior and survival advantages by brain tumor cells during disease progression. Therefore, the simultaneous targeting of these oncogenic signaling components including wild-type EGFR, EGFRvIII mutant and hedgehog pathways may constitute a potential therapeutic approach of great clinical interest to eradicate BTICs and improve the efficacy of current clinical treatments by radiation and/or chemotherapy against aggressive and recurrent medulloblastomas and GBMs.

Original languageEnglish (US)
Pages (from-to)479-500
Number of pages22
JournalBrain Pathology
Issue number5
StatePublished - Sep 1 2011



  • EGFR
  • brain tumor-initiating cells
  • carcinogenesis
  • combination therapy
  • glioblastoma multiforme
  • hedgehog
  • medulloblastomas
  • molecular targeting
  • receptor tyrosine kinases

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

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