Why do patients with head and neck squamous cell carcinoma experience distant metastases: can they be prevented?

This article will examine recent publications that enhance our understanding of this process, and current areas of investigation for therapeutic intervention in preventing and treating metastatic disease.

Recent investigations have led to insights into the mechanisms of cellular adhesion, invasion, and angiogenesis. E-cadherin, integrins, and selectins are all pivotal in cell-cell adhesion and communication. Recent advances in the area of tumor angiogenesis have led to our discovery of endostatin, an anti-angiogenic peptide that has potential in treating metastatic head and neck cancer. Current trials looking at sentinel node mapping may allow us to evaluate the nodal status of early head and neck cancer and identify a subset of patients at risk for distant metastasis.

As our understanding of metastatic disease increases, so will our ability to intervene in the various pathways involved in metastatic evolution. Metastatic cells are likely to respond differently to chemotherapeutic agents. Agents inhibiting specific aspects of invasion, adhesion, and angiogenesis will need to be combined to intervene at these key steps. Continued investigation into the biology of the epidermal growth factor receptor has led to an increased understanding of the mechanisms of abrogation of apoptosis, increased cellular motility, and metastasis. Inhibition of the epidermal growth factor receptor pathway with the monoclonal antibody C-255 has been shown to inhibit these processes and will likely be effective in reducing the development of distant metastasis.