Novel therapeutic target for head and neck squamous cell carcinoma: HGF-MET signaling pathway

Head and neck squamous cell carcinoma (HNSCC) represents a devastating type of malignancy characterized by its high incidence of regional and distant metastases at the time of diagnosis. Vital physiological functions in the upper aerodigestive tract are often impaired as a result of the disease and treatment for the disease, giving rise to severe morbidity in patients suffering from this type of cancer. It is crucial to delineate the aberrant growth signaling pathways in HNSCC cells and develop specific target therapies for the disease to improve the treatment outcome. Although the epidermal growth factor receptor pathway has been extensively studied in HNSCC and anti-epidermal growth factor receptor therapy has already shown promise in treating HNSCC in phase III clinical trials, the signaling pathway that accounts for the highly invasive phenotype of HNSCC needs to be defined and also therapeutically targeted. The hepatocyte growth factor-MET signaling pathway has been studied extensively over the past two decades and it is now clear that it plays an important role in mediating invasive growth of many types of cancer. Here, we review comprehensively the evidence on hepatocyte growth factor-MET cascade being a key in the signaling pathway in mediating invasive growth of HNSCC and the potential of this signaling pathway to be a therapeutic target for the treatment of HNSCC.