Epidermal growth factor receptor as a therapeutic target in glioblastoma

Neuromolecular Med. 2013 Jun;15(2):420-34. doi: 10.1007/s12017-013-8229-y. Epub 2013 Apr 11.


Glioblastoma represents one of the most challenging problems in neurooncology. Among key elements driving its behavior is the transmembrane epidermal growth factor receptor family, with the first member epidermal growth factor receptor (EGFR) centered in most studies. Engagement of the extracellular domain with a ligand activates the intracellular tyrosine kinase (TK) domain of EGFR, leading to autophosphorylation and signal transduction that controls proliferation, gene transcription, and apoptosis. Oncogenic missense mutations, deletions, and insertions in the EGFR gene are preferentially located in the extracellular domain in glioblastoma and cause constitutive activation of the receptor. The mutant EGFR may also transactivate other cell surface molecules, such as additional members of the EGFR family and the platelet-derived growth factor receptor, which ignite signaling cascades that synergize with the EGFR-initiated cascade. Because of the cell surface location and increased expression of the receptor along with its important biological function, EGFR has triggered much effort for designing targeted therapy. These approaches include TK inhibition, monoclonal antibody, vaccine, and RNA-based downregulation of the receptor. Treatment success requires that the drug penetrates the blood-brain barrier and has low systemic toxicity but high selectivity for the tumor. While the blockade of EGFR-dependent processes resulted in experimental and clinical treatment success, cells capable of using alternative signaling ultimately escape this strategy. A combination of interventions targeting tumor-specific cell surface regulators along with convergent downstream signaling pathways will likely enhance efficacy. Studies on EGFR in glioblastoma have revealed much information about the complexity of gliomagenesis and also facilitated the development of strategies for targeting drivers of tumor growth and combination therapies with increasing complexity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics
  • Brain Neoplasms / therapy
  • Cancer Vaccines
  • Cell Transformation, Neoplastic
  • Clinical Trials as Topic
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / immunology
  • Gene Expression Regulation, Neoplastic
  • Genetic Therapy
  • Glioblastoma / drug therapy*
  • Glioblastoma / enzymology
  • Glioblastoma / genetics
  • Glioblastoma / therapy
  • Humans
  • Molecular Targeted Therapy*
  • Mutation
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology
  • Oligonucleotides, Antisense / therapeutic use
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein Processing, Post-Translational / drug effects
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Catalytic / therapeutic use
  • RNA, Small Interfering / therapeutic use
  • Signal Transduction / drug effects


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Cancer Vaccines
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Oligonucleotides, Antisense
  • Protein Kinase Inhibitors
  • RNA, Catalytic
  • RNA, Small Interfering
  • ErbB Receptors