Molecular Determinants of Head and Neck Cancer

Head and neck cancers, involving sites from the nasopharynx to the subglottic larynx, are frequently devastating cancers that afflict patients around the world. These cancers are frequently locally advanced prior to detection, and require multimodality therapy that is associated with high morbidity. As this book addresses this difficult disease, it accomplishes three main goals.

First, it introduces the etiology and subclasses of squamous cell carcinomas of the head and neck (SCCHNs), and how these factors affect prognosis. Although habitual exposures to tobacco, alcohol, and other agents have historically been the main causes of SCCHN, a rising proportion of oropharynx cancers arise from transforming human papillomavirus (HPV) infection. These two broad classes of SCCHN have significant differences in disease profile and response to treatment, as we discuss.

Second, it summarizes the current state of understanding of the genetic, epigenetic and protein expression changes associated with the various classes of SCCHN. In the past decade, disease pathogenesis of SCCHN has been appreciated to involve deregulation of multiple tumor pathways, including the receptor tyrosine kinases (RTKs) EGFR, ERBB2, ERBB3, c-MET, and IGF1R; transforming growth factor β (TGFβ); Notch; cytoplasmic signaling proteins including PTEN, PI3K, JAK/STAT, and Wnt-responsive β-catenin; mutation control systems, including p53 and the DNA damage repair (DDR) machinery; and hypoxic response. The specific understanding of the action of these proteins in SCCHN is presented here.

Finally, this book defines potential therapeutic targets for improved management of the disease in the future, discussing prospects for improved prediction ofprognosis.