Purpose: To present an overview of the significance of erbB tyrosine kinase family members as prognostic-predictive factors and as targets of therapeutic intervention in patients with head-and-neck carcinomas (HNCs).
Methods and materials: The data of clinical studies addressing the correlation between the expression of erbB family tyrosine kinases, particularly epidermal growth factor receptor (EGFR), and the prognosis and pattern of failure were reviewed, along with the response of HNCs to EGFR antagonists such as a chimeric monoclonal antibody and a couple of small molecule tyrosine kinase inhibitors.
Results: Correlative biomarker studies showed that most HNCs express high levels of EGFR and/or other members of the erbB family. Several studies have demonstrated that patients with EGFR-overexpressing tumors had significantly worse overall survival. Compelling evidence has emerged showing that EGFR-overexpressing HNCs respond more poorly to radiotherapy (RT), although data of its impact on the response to chemotherapy are scarce. Clinical studies have so far showed that tyrosine kinase inhibitors have rather limited antitumor activities when given alone. Stimulated by promising preclinical data, the value of EGFR antagonists in the combined modality setting, particularly with RT, is being addressed in clinical trials.
Conclusion: Members of the erbB receptor tyrosine kinase family, particularly EGFR, were found to be a strong biomarker for poor prognosis and HNC resistance to RT. The available data showed that EGFR antagonists given as single modality therapies yield rather limited antitumor activity. The results of trials testing the efficacy of combining EGFR antagonist with RT or chemotherapy will emerge within the next few years.