title: The type III epidermal growth factor receptor mutation. Biological significance and potential target for anti-cancer therapy.
abstract: Mutations in the epidermal growth factor receptor occur frequently in a number of human tumours including gliomas, non-small-cell lung carcinomas, ovarian carcinomas and prostate carcinomas. The type III epidermal growth factor receptor mutation (variously named EGFRvIII, de2-7 EGFR or AEGFR), which lacks a portion of the extracellular ligand binding domain, is the most common. Here, we review the current status with regard to the role of EGFRvIII in human cancers. A detailed discussion of the formation of EGFRvIII and its structure at the protein level are likewise included along with a discussion of its more functional roles. The design and use (preclinical and clinical) of small molecule inhibitors, antibodies, and antisense oligonucleotides against wild-type EGFR are considered in detail as these strategies can be directly adapted to target EGFRvIII. Finally, the status of EGFRvIII targeted therapy is reviewed.
authors.affiliation: Department of Radiation Biology, The Finsen Centre, National University Hospital, Copenhagen, Denmark.
authors.forename: M W
authors.initials: MW
authors.lastname: Pedersen
authors.forename: M
authors.initials: M
authors.lastname: Meltorn
authors.forename: L
authors.initials: L
authors.lastname: Damstrup
authors.forename: H S
authors.initials: HS
authors.lastname: Poulsen
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D001483:Base Sequence; D066246:ErbB Receptors / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051020:bcl-X Protein
chemical_list: D000911:Antibodies, Monoclonal; C494811:BCL2L1 protein, human; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors