EGFR as a Target for Glioblastoma Treatment: An Unfulfilled Promise

CNS Drugs. 2017 Sep;31(9):723-735. doi: 10.1007/s40263-017-0456-6.

Abstract

The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibodies against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled. This review analyses the attempts to use TKIs and monoclonal antibodies against glioblastoma, with special consideration given to immunological approaches, the use of EGFR as a docking molecule for conjugates with toxins, T-cells, oncolytic viruses, exosomes and nanoparticles. Drug delivery issues associated with therapies for intracerebral diseases, with specific emphasis on convection enhanced delivery, are also discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Drug Delivery Systems
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / antagonists & inhibitors
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / administration & dosage
  • Protein Kinase Inhibitors / pharmacology

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Epidermal Growth Factor
  • ErbB Receptors