Table of Contents Author Guidelines Submit a Manuscript
Journal of Oncology
Volume 2009, Article ID 896407, 12 pages
http://dx.doi.org/10.1155/2009/896407
Review Article

Improving Response Rates to EGFR-Targeted Therapies for Head and Neck Squamous Cell Carcinoma: Candidate Predictive Biomarkers and Combination Treatment with Src Inhibitors

1Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA 15213, USA
2Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15213, USA
3Eye and Ear Institute, Suite 500 200 Lothrop Street, Pittsburgh, PA 15213, USA

Received 14 April 2009; Accepted 17 May 2009

Academic Editor: Paul Harari

Copyright © 2009 Ann Marie Egloff and Jennifer Rubin Grandis. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The epidermal growth factor receptor- (EGFR-) directed antibody, cetuximab, was FDA-approved for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 2006. Additional EGFR-targeting agents in clinical development for SCCHN include other EGFR-directed antibodies, tyrosine kinase inhibitors and antisense DNA. Although the majority of SCCHN overexpress EGFR, SCCHN clinical responses to EGFR-targeting agents have been modest. Molecular predictors for SCCHN response to EGFR-targeted therapies have not been identified. However, molecular correlate studies in lung cancer and colon cancer, which have EGFR-targeted therapeutics FDA-approved for treatment, may provide insights. We describe candidate predictive markers for SCCHN response to EGFR-targeted therapies and their prevalence in SCCHN. Clinical response will likely be improved by targeted therapy combination treatments. Src family kinases mediate EGFR-dependent and -independent tumor progression pathways in many cancers including SCCHN. Several Src-targeting agents are in clinical development for solid malignancies. Molecular correlate studies for Src-targeting therapies are few and biomarkers correlated with patient response are limited. Identifying SCCHN patients who will respond to combined EGFR- and Src-targeting will require further characterization of molecular correlates. We discuss rationale for EGFR and Src co-targeting for SCCHN treatment and describe recent clinical trials implementing combined Src- and EGFR-targeted therapeutics.