Molecular Determinants of Head and Neck Cancer

1. Front Matter

   Pages i-ix

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2. Overview: The Pathobiology of Head and Neck Cancer

   • Barbara Burtness, Erica A. Golemis

   Pages 1-5

3. Molecular Features and Treatment Modalities of “Classic” Versus Human Papilloma Virus-Associated Head and Neck Cancer

   • Giannis Mountzios, Amanda Psyrri

   Pages 7-21

4. Epidemiology of HPV in Head and Neck Cancer: Variant Strains, Discrete Protein Function

   • Camille C. R. Ragin, Jeffrey C. Liu

   Pages 23-53

5. EGFR Inhibitors as Therapeutic Agents in Head and Neck Cancer

   • Hanqing Liu, Jennifer R. Cracchiolo, Tim N. Beck, Ilya G. Serebriiskii, Erica A. Golemis

   Pages 55-90

6. The Role of HGF/c-MET in Head and Neck Squamous Cell Carcinoma

   • Tanguy Y. Seiwert, Tim N. Beck, Ravi Salgia

   Pages 91-111

7. Insulin-Like Growth Factor-1 Receptors in Head and Neck Cancer

   • Steven A. Rosenzweig, Casey O. Holmes

   Pages 113-130

8. The PI3K Signaling Pathway in Head and Neck Squamous Cell Carcinoma

   • Jason D. Howard, Christine H. Chung

   Pages 131-161

9. Jak/STAT Signaling in HNC

   • Bhavana S. Vangara, Jennifer R. Grandis

   Pages 163-177

10. TGFβ Regulates EMT in Head and Neck Cancer

    • Jill M. Neiman, Xiao-Jing Wang

    Pages 179-197

11. The Wnt/β-catenin Signaling Circuitry in Head and Neck Cancer

    • Rogerio M. Castilho, J. Silvio Gutkind

    Pages 199-214

12. Human Papillomavirus (HPV)-Positive Head and Neck Cancer and the Wnt Signaling Pathway

    • Theodoros Rampias, Amanda Psyrri

    Pages 215-225

13. p53 in Head and Neck Cancer

    • Jong-Lyel Roh, Wayne M. Koch

    Pages 227-258

14. DNA Damage Proteins and Response to Therapy in Head and Neck Cancer

    • Ranee Mehra, Ilya G. Serebriiskii

    Pages 259-282

15. Hypoxia and Radioresistance in Head and Neck Cancer

    • Peiwen Kuo, Quynh-Thu Le

    Pages 283-302

16. Sequencing HNC: Emergence of Notch Signaling

    • Curtis R. Pickering, Thomas J. Ow, Jeffrey N. Myers

    Pages 303-323

17. Gene Expression in HNC

    • Michael F. Ochs, Joseph A. Califano

    Pages 325-341

18. Projections: Novel Therapies for HPV-Negative Cancers of the Head and Neck

    • Barbara Burtness

    Pages 343-359

19. Back Matter

    Pages 361-362

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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.

• Dna repair
• Human Papillomavirus
• genomics
• head and neck cancer
• hypoxia
• molecular determinants

• Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, USA

  Barbara Burtness, Erica A. Golemis

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.

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