Molecular therapy in head and neck oncology.

Therapeutic management of locally advanced, recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is often limited by a rather unfavorable efficacy and toxicity ratio. Since the 1990s, targeted molecular therapy has been extensively investigated both as a single modality and in combination with cytotoxic treatments, such as radiotherapy or chemotherapy. EGFR is commonly over expressed in HNSCC and is an attractive molecular target. The EGFR signaling pathway is involved in a variety of cellular responses including cell growth and proliferation, and monoclonal antibodies and small-molecule inhibitors have been developed to inhibit EGFR pathways. Agents that target angiogenesis have also been tested in combination with EGFR inhibitors. A number of phase I/II and phase III studies have demonstrated that patients with high-risk HNSCC or those receiving palliative treatment for recurrent or metastatic disease benefit from the addition of EGFR inhibitors to chemotherapy and radiotherapy. This Review discusses the rationale for using targeted therapies based on inhibition of EGFR and angiogenesis, and describes the most recent preclinical and clinical evidence of the important role for targeted therapies in the management of head and neck cancers.