Autophagic action of new targeting agents in head and neck oncology

The survival rates of patients with squamous cell carcinoma of the head and neck (HNSCC) have not improved significantly despite multi-modality therapy, including surgery, radiation therapy and chemotherapy. Recently, molecular targeted agents have shown significant improvement in clinical outcomes; for example, in chronic myelogeneous leukemia with imatinib, breast cancer with trastuzumab, colon cancer with bevacizumab and cetuximab, and renal cell cancer with sorafenib and sunitinib. In HNSCC, the epidermal growth factor receptor antibody cetuximab has shown promising results in combination with radiation. Targeted agents including cetuximab induce stresses to activate prosurvival autophagy. Combining autophagy inhibitors with agents that induce autophagy as a prosurvival response may therefore increase their therapeutic efficacy. Whether autophagy contributes to the prosurvival response or to the antitumor effect of chemotherapeutic drugs is largely unknown. This review will discuss the possible role of autophagy as a novel target for anticancer therapy agents in HNSCC.