BELGIAN JOURNAL OF MEDICAL ONCOLOGY VOL . 2 ISSUE 3 - 2008 161 Introduction As 90% of all cases of squamous cell cancer of the head and neck (SCCHN) show overexpression of EGFR, there is a strong rationale supporting Epi- dermal Growth Factor Receptor (EGFR) target- ing in this malignancy. his rationale is furt her strengthened by the fact that EGFR overexpres- sion is associated with a worse prognosis. 1,2 he EGFR molecule consists of an N-terminal, ex- tracellular, ligand-binding domain; a hydropho- bic, transmembrane domain and a C-terminal, intracellular domain with tyrosine kinase activity (Figure 1 on page 162). he EGFR can be stimu- lated by several growth factors, such as transform- ing growth factor (TGF)- α and epidermal growth factor (EGF), which bind to the extracellular do- main of the receptor. his ligand binding results in EGFR dimerization and activation of the tyro- sine kinase domains present on each receptor. his kinase activation results in cross-phosphorylation of tyrosine residues on each member of the recep- tor pair and initiates the formation of signalling complexes in the cytoplasm which can translocate to the cell nucleus and activate gene transcription. his editing of gene transcription eventually re- sults in the induction of several cellular responses such as cell proliferation. Ultimately, receptor– ligand complexes are internalised and the signal is terminated. 3 Nowadays there are two EGFR targeting strategies used in clinical practice: monoclonal antibodies (MAbs) directed at the extracellular domain of the receptor and small molecule, ATP-competitive ty- rosine kinase inhibitors. 4,5 he use of both modali- ties in the treatment of SCCHN is currently under investigation. hus far, the monoclonal EGFR an- tibody cetuximab has been studied in most detail. Cetuximab is a human-murine chimeric immu- noglobulin G 1 (IgG 1 ) monoclonal antibody which competitively binds to the extracellular domain of the EGFR preventing activation of the receptor by endogenous ligands. he antibody-receptor complex is internalized and degraded resulting in a down regulation of the EGFR expression. Cetuximab in head and neck cancer Cetuximab has been tested in metastatic and/or re- current SCCHN, both in irst line, in combination with platinum-based chemotherapy, as in second line after failure of platinum-based chemotherapy. Cetuximab has also been tested in association with radiation as deinitive treatment for locoregionally advanced SCCHN. Summary As EGFR is overexpressed in over 90% of all squa- mous cell cancers of the head and neck (SCCHN) there is a strong rationale supporting Epidermal Growth Factor Receptor (EGFR) targeted therapies in SCCHN. The first monoclonal EGFR directed antibody that entered the clinic is cetuximab. The role of this drug in the treatment of recurrent and/or metastatic disease either in first line, in combination with platinum-based chemotherapy, or in second line, after failure of platinum-based chemotherapy, is well established. However, its place in the treatment of locoregionally advanced SCCHN is less clear due to the fact that up to now there has not been a study comparing cetuximab with chemoradiation which is currently the stand- ard care in this setting. (BJMO 2008;vol 2;3:161-7) The role of cetuximab in the treatment of head and neck cancer P. Specenier, J. Vermorken Cetuximab, head and neck cancer, EGFR Authors Key words O N C O T H E R A P Y U P D A T E