Molecular Determinants of Head and Neck Cancer

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. It is estimated that approximately 50,000 patients develop head and neck cancer annually in the United States, of whom approximately 50% succumb to this cancer. For most cases of SCCHN, treatment is multimodal, often combining surgery or irradiation with chemotherapy; even successfully treated patients frequently experience durable and severe side effects. Improving cure rates and reducing chronic morbidity are urgent clinical needs for head and neck cancer. However, in contrast to cancer types such as breast or prostate that have been much studied and have well-defined biology, until recently, relatively few researchers investigated the molecular basis of HNC, making it difficult to design targeted treatments with better efficacy and less debilitating side effects.

This volume will provide an overview of the factors contributing to disease pathogenesis, including the recognition of discrete molecular subtypes with distinct etiology, prognosis, and treatment response. This volume will familiarize the reader with the critical signaling pathways and oncogenic drivers for HNC. It will outline the differences between HPV-positive and HPV-negative disease, and how these differences affect treatment choice and outcome. The book will emphasize developments in the past five years, including the growing understanding of the genomic and epigenomic features of the disease based on analysis of next generation sequencing (NGS) data, and timely topics such as the analysis of HNC stem cell populations, non-coding mRNAs, and inflammatory response. It will address exciting new therapeutic approaches such as the use of immunotherapies to treat HNC patients. Overall,the book will provide the reader with current understanding of the biology and treatment of the disease, and describe timely questions that will guide future research aimed at controlling and curing this disease.

Auteur

Barbara Burtness, M.D. is Professor of Medicine, Yale University School of Medicine and Co-Leader, Developmental Therapeutics Program, Yale Cancer Center. As Chair of the Head and Neck Committee in 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 and Co-leader of the Program in Molecular Therapeutics at the Fox Chase Cancer Center. 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 to effect disease control and cure.

Contenu

Chapter 1: Overview: B. Burtness and E. Golemis

Chapter 2: HER inhibition in HNC: E. Golemis and B. Burtness

Chapter 3: MET: T Beck, Fox Chase Cancer Center

Chapter 4: PI3K/mTOR/AMPK: C. Chung, Moffit Cancer Center

Chapter 5: Jak/STAT: J.R. Grandis, UCSF Chapter 6: TGFb: Neiman and Wang, University of Colorado

Chapter 7: Wnt and catenin Signaling: MA Kukurusinska, Boston University

Chapter 8: P53/p63/p73: B. Burtness

Chapter 9: DNA damage: R. Bindra, Yale University

Chapter 10: APOBEC Proteins: K.S. Anderson, Yale University Chapter 11: Hypoxia, including HIF1: Q. Le, Stanford University

Chapter 12: VEGF/Angiogenesis and Antiangiogenic Therapy: A Argiris, Thomas Jefferson University

Chapter 13: Sequencing/genomic insights: J.Myers, MD Anderson

Chapter 14: Gene expression, Methylation, and histones: R.Mehra, A.Andrews, S.Peri, Fox Chase Cancer Center and A.Bhatia, Yale University

Chapter 15: Inflammation: Carter Van Waes, NIH

Chapter 16:Immunotherapy: Ferris and Baumann, UPMC

Chapter 17: FAK/Integrin pathway inhibitors: Nils Cordes, Dresden

Chapter 18: Targeting cell cycle controls: E.Golemis

Chapter 19: Head and neck cancer stem cells: L.Bourguignon, UCSF

Chapter 20: Non-coding RNAs: C.Punyadeera, Queensland University

Chapter 21: Epidemiology of HPV: Ragin and Lui, Fox Chase Cancer Center Chapter 22: DNA damage in HPV-positive SCCHN: WG Yarbrough, Yale University

Chapter 23: Treatment paradigms in HPV-positive SCCHN: A Cmelak, Vanderbilt University