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

EGFR as a Target for Glioblastoma Treatment: An Unfulfilled Promise

Manfred Westphal  1 , Cecile L Maire  2 , Katrin Lamszus  2
Affiliations
Review

EGFR as a Target for Glioblastoma Treatment: An Unfulfilled Promise

Manfred Westphal et al. CNS Drugs. 2017 Sep.

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.

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Conflict of interest statement

Funding

The open access fee was paid by the Department of Neurosurgery, University Hospital Hamburg, Hamburg, Germany. No specific funding for this work was received.

Conflict of interest

The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Integrative sketch of epidermal growth factor receptor (EGFR) targeted treatment modalities and additional technologies. Focused ultrasound may be combined with EGFR-targeted nanoparticles to result in local release of cargo; likewise, boronated EGFR binding compounds will only be active (small flashes) in the field of a neutron beam. The sketch also illustrates the heterogeneity of the different types of EGFR expression including the mutation types and amplification patterns. The tumor is made up of cells heterogeneous in their EGFR expression and alterations as indicated by the different cell types (see text). To improve unsatisfactory intravenous delivery, delivery of large molecules or even viruses to the tumor (dark pink) or the invasive zone (light pink) convection (CED) is a suitable technique as indicated by the two porous catheter tips in the top part of the figure. BBB blood–brain barrier, BNCT boron neutron capture therapy, CAR chimeric antigen receptor, EGFRvIII epidermal growth factor receptor variant III, EGFRwt/mut epidermal growth factor receptor wild-type/mutant, mABs monoclonal antibodies, RTK receptor tyrosine kinase, HSR homogeneously staining region
See this image and copyright information in PMC

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