Emerging role of EGFR-targeted therapies and radiation in head and neck cancer.

The treatment of head and neck cancer has been at the forefront of novel therapeutic paradigms. The introduction of drugs that interact with selective biologic pathways in the cancer cell has generated considerable attention recently. A wide variety of new compounds that attempt to target growth-signaling pathways have been introduced into the clinic. A majority of studies in the clinic have focused on epidermal growth factor receptor (EGFR) antagonists, but future studies will likely build upon or complement this strategy with agents that target angiogenic or cell-cycle pathways. EGFR activation promotes a multitude of important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Since radiation therapy plays an integral role in managing head and neck squamous cell cancer (HNSCC), inhibiting the EGFR pathway might improve our efforts at cancer cure. The challenge now is to understand when the application of these EGFR inhibitors is relevant to an individual patient and how or when these drugs should be combined with radiation or chemotherapy. Are there molecular markers available to determine who will respond to EGFR inhibitors and who should be treated with alternative approaches? What are the mechanisms behind intrinsic or acquired resistance to targeted agents, and how do we prevent this problem? We need to formulate integrated laboratory/clinical research programs that address these important issues.