New advances in targeted therapies for squamous cell carcinoma of the head and neck.

Several molecular pathways are deregulated and activated in squamous cell carcinoma of the head and neck making this disease attractive for targeted molecular therapies. Cetuximab, a monoclonal antibody that binds to the epidermal growth factor receptor, improves the overall survival when combined with radiation therapy or chemotherapy. Novels agents targeting different molecular pathways in squamous cell carcinoma of the head and neck are currently under development. Among them, dual (epidermal growth factor receptor/human epidermal growth factor receptor-2) or pan-human epidermal growth factor receptor inhibitors and drugs that target the insulin growth factor-1 receptor, the MET receptor, or the phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway have shown either interesting preclinical activity or promising preliminary clinical efficacy. Angiogenesis inhibitors should be used with caution in squamous cell carcinoma of the head and neck due to the risk of tumor bleeding. However, only a minority of patients seems to benefit from these new approaches. Understanding the primary and acquired resistance mechanisms to predict the treatment efficacy is of crucial importance to allow a better patient selection.