Abstract
Squamous cell carcinoma of head and neck (SCCHN) is the most common neoplasm of the upper aerodigestive tract. In this paper, we attempt to summarize the role and applications of the epidermal growth factor receptor (EGFR) inhibitors monoclonal antibodies (moAbs) and tyrosine kinase inhibitors (TKIs) locally advanced as well as metastatic SCCHN. Targeted therapy in SCCHN is now incorporated in the first-line regimes for advanced disease. Novel targeted agents, including the EGFR antibody, cetuximab, have been approved for use as single agents or in combination with radiation therapy or chemotherapy in treatment of recurrent metastatic or locally advanced SCCHN. Refractory mechanisms that bypass the pathway of EGFR inhibitors activity are identified explaining resistance to targeted therapy. Strategies of cotargeting EGFR and other pathways are under investigation. Examples of targeted therapy being used include mammalian target of rapamycin (mtor) inhibitors, antivascular endothelial growth factor (VEGF) moAb, and other inhibitors. We will be focusing our paper on the preclinical and clinical aspects of EGFR inhibition in SCCHN and touch upon other targeted therapies in application.
Highlights
It is estimated that about 49,260 new cases of the oral cavity, pharyngeal and laryngeal cancers and 11,480 cancer deaths occurred in 2010 [1]
Similar to Remiers et al findings, Kumar et al studied the correlations of Human Papilloma Virus (HPV-)DNA, p16, epidermal growth factor receptor (EGFR), and other variables, it was found that EGFR expression was inversely associated with response to induction chemotherapy (P: 0.01), chemotherapy/radiotherapy (P: 0.055), overall survival (P: 0.001), and disease-specific survival (P: 0.002) and was directly associated with current smoking (P: 0.04), female sex (P: 0.053), and lower HPV titer (P: 0.03) [24]
Cetuximab is a human murine MoAb of the immunoglobulin G1 (IgG1) isotype that appears to act through multiple mechanisms, and, as an anti-EGFR MoAb, cetuximab blocks the binding of natural ligands to the EGFR, preventing EGFR dimerization, internalization, and autophosphorylation and inhibiting subsequent activation of tyrosine-kinasemediated signaling pathways
Summary
It is estimated that about 49,260 new cases of the oral cavity, pharyngeal and laryngeal cancers and 11,480 cancer deaths occurred in 2010 [1]. The EGFR is the cell-surface receptor for members of the epidermal growth factor (EGF) family of extracellular protein ligands. It is a member of the ErbB family of receptors, a subfamily of four closely related receptor tyrosine kinases: Journal of Oncology. Autophosphorylation of several tyrosine residues in the Cterminal domain of EGFR occurs This autophosphorylation elicits downstream activation and signaling by several other proteins that associate with the phosphorylated tyrosines through their own phosphotyrosine-binding SH2 domains. Inhibition of the extracellular domain of the receptor with MoAbs prevents activation of the receptor by endogeneous ligands through competitive inhibition; it results in internalization and degradation of the antibody-receptor complex, downregulating EGFR expression.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
