Overview of epidermal growth factor receptor biology and its role as a therapeutic target in human neoplasia

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Abstract

The ability of the epidermal growth factor receptor (EGFR) to transform epithelial cells, the overexpression of EGFR and its ligands in several human carcinomas, and the causal association of the receptor network with accelerated tumor progression provided a rationale for targeting this signaling system with tumor-selective strategies. Two of these antireceptor approaches, both based on the known structure/function of the EGFR, will be discussed. The first strategy involved the development of humanized monoclonal antibodies against the nonconserved receptor's extracellular domain. These antibodies block ligand binding and can induce receptor downregulation. The second approach was the generation of adenosine triphosphatemimetics that compete with adenosine triphosphate for binding to the receptor's kinase pocket and disable the ability of the EGFR to transduce intracellular signals. Early clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, alter the natural history of EGFR-expressing cancers with little toxicity to the tumor-bearing host.

Original languageEnglish (US)
Pages (from-to)3-9
Number of pages7
JournalSeminars in oncology
Volume29
Issue number5 SUPPL. 14
StatePublished - Oct 2 2002

ASJC Scopus subject areas

  • Hematology
  • Oncology

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