Therapeutic targets in head and neck squamous cell carcinoma: identification, evaluation, and clinical translation.

Head and neck squamous cell carcinoma (HNSCC) encompasses a diverse group of malignancies originating in the oral cavity, oropharynx, larynx and hypopharynx. Although treatment modalities have improved, carefully designed biomarker-driven clinical trials will yield the best opportunities to enhance HNSCC therapy options in the future. Due to the heterogeneous nature of HNSCC, discovering a "silver bullet" for the treatment of HNSCC is unlikely. Consequently, impactful HNSCC clinical trials will require multiple assay platforms and expanded technical expertise. In this review, we will outline pathways critical to HNSCC oncogenesis and highlight signaling nodes within these pathways that represent biomarkers for prognosis and potential targeted therapies. All treatment modalities are subject to mechanisms of resistance; thus, lessons learned from HNSCC investigations and studies of similar targeted agents in other pertinent malignancies will be discussed.