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 ß (TGFß); Notch; cytoplasmic signaling proteins including PTEN, PI3K, JAK/STAT, and Wnt-responsive ß-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.

Autorentext

Barbara Burtness, M.D. is Associate Director for Clinical Research at the Fox Chase Cancer Center. She is also a co-leader of the Keystone Program in Head and Neck Cancer. As Chair of the Head and Neck Committee in the Eastern Cooperative Oncology Group and a member of the NCI Head and Neck Steering Committee, she helps shape the national agenda for research on all stages of head and neck cancer.

Erica Golemis, Ph.D. is the Deputy Chief Scientific Officer at the Fox Chase Cancer Center. She is also the Co-Leader of Developmental Therapeutics and Co-Leader of the Head and Neck Cancer Keystone at Fox Chase. Her research seeks to define the changes in cell signaling that occur as tumors spread by metastasis and develop resistance to drugs, with the ultimate goal of inhibiting these processes.

Zusammenfassung
Squamous cell cancers of the head and neck (SCCHN), also known as head and neck cancers (HNC) encompass malignancies of the oral cavity, larynx, nasopharynx and pharynx, and are diagnosed in over 500,000 patients worldwide each year, accounting for 5% of all malignancies. In the past several years, there have been significant developments in understanding of HNC. It is now recognized that although alcohol and tobacco use has represented the likely predominant cause of SCCHN, the incidence of a second class of SCCHN related to oncogenic human papillomavirus (HPV) infection is increasing, with a four-fold increase in the past 2 decades, and now thought to represent up to 30% of cases. The first effective target for SCCHN, the EGFR-targeting antibody cetuximab, was approved as recently as in 2006; since then, a growing body of research has identified additional signaling pathways as important in disease pathogenesis, and in resistance to treatment. Proteins such as c-Met, Src, and HER2 are emerging as new therapeutic targets, with a considerable ferment in the clinical trial community. As a capstone of research progress, 2011 marked the first reports of high throughput sequencing of SCCHN tumors, with these efforts identifying unexpected players such as Notch as frequent subject of mutation, spawning new hypotheses for future research. This book will be of interest to researchers who are interested in better understanding the biology of head and neck cancers, with the goals of better designing therapies, identifying risk factors, or investigating the molecular basis of the disease.

Inhalt
Overview: The Pathobiology of Head and Neck Cancer.- Human papillomavirus (HPV)-positive head and neck cancer and the Wnt signaling pathway.- EGFR Inhibitors as Therapeutic Agents in Head and Neck Cancer.- The Role of HGF/c-MET in Head and Neck Squamous Cell Carcinoma.- Insulin-like Growth Factor-1 Receptors in Head and Neck Cancer.- The PI3K Signaling Pathway in Head and Neck Squamous Cell Carcinoma.- Jak/STAT Signaling in HNC.- TGF regulates EMT in head and neck cancer.- p53 in Head and Neck Cancer.- DNA damage proteins and response to therapy in head and neck cancer.- Hypoxia and radioresistance in head and neck cancer.- The Wnt -catenin Signaling Circuitry in Head and Neck Cancer.- Sequencing HNC: Emergence of Notch Signaling.- Gene Expression in HNC.- Epidemiology of HPV in Head and Neck Cancer; variant strains, discrete protein function.- Projections: Novel Therapies for HPV-Negative Cancers of the Head and Neck.- Index.