EGFR function and detection in cancer therapy.

Abstract

There is strong evidence to support targeting the epidermal growth factor receptor (EGFR) for cancer therapy. Monoclonal antibodies targeting the ligand-binding region of the receptor and receptor tyrosine kinase inhibitors have shown promising results in subgroups of patients. Although the EGFR appears to have prognostic significance in many solid tumors, the lack of predictive capability of EGFR assessment using immunohistochemistry (IHC) in clinical trials of EGFR inhibitors has raised concerns about the selection of patients for therapy and emphasizes the need for consistency in the use of a reliable and highly sensitive detection method for this receptor. It is possible that the predictive significance of EGFR expression has been underestimated because of the relatively poor sensitivity of IHC as a detection method, the lack of standardization of IHC assays and interpretation between studies, and the lack of consistent evaluation of activated (phosphorylated) receptors. A more comprehensive approach that encompasses evaluation of the entire EGFR network, including measurement of tumor levels of the receptor (activated and nonphosphorylated), its ligands, and dimerization partners, as well as downstream effector molecules and receptor mutations, may be needed in order to more appropriately select patients for therapy.