Mutant epidermal growth factor receptors as targets for cancer therapy.
The epidermal growth factor (EGF) receptor is overexpressed in many cancers, and is under intensive investigation as a target for cancer therapy. Cancer cells have also been shown to express mutated EGF receptors; these are potentially highly specific targets for cancer therapeutics, as they have not been detected in any normal adult tissues. The most common of these mutant EGF receptors, EGFRvIII, is one in which amino acids 6 - 273 of the extracellular domain are deleted. This specific mutation is common in glioblastoma and in several other types of cancer, and has been shown to promote aggressive growth of tumors in vivo. The loss of part of the extracellular domain results in a receptor that has constitutive tyrosine kinase activity. Current evidence suggests that EGFRvIII has altered signalling properties compared to normal EGF receptor. The mutation in EGFRvIII also creates a new, cancer cell-specific epitope. This epitope is extracellular and therefore represents a very promising target for antibody-directed therapeutics. This review covers our current understanding of the properties of EGFRvIII, and recent developments in the characterization and therapeutic application of EGFRvIII-specific antibodies.
Ottawa Regional Cancer Centre, Centre for Cancer Therapeutics, 503 Smyth Road, Ottawa, Ontario, Canada, K1H 1C4. Ian.Lorimer@orcc.on.ca
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D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D066246:ErbB Receptors / Q000187:drug effects* / Q000235:genetics* / Q000276:immunology; D018390:Gene Targeting; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D019275:Radiopharmaceuticals; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; D066246:ErbB Receptors