Author: Alice N. Weaver
Publisher:
ISBN:
Category :
Languages : en
Pages : 191
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Book Description
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high rates of recurrence and mortality. Unlike other cancer types, genome sequenc-ing studies have failed to produce clinically actionable targets to improve HNSCC man-agement. Therefore, alternative methods are needed to study the molecular mechanisms responsible for disease progression and response to therapy. The focus of this research was to determine how dysregulation of cell signaling pathways affects outcomes in HNSCC. In HPV-positive HNSCCs, we hypothesized that HPV induces dysregulation of the DNA damage response which mediates differences in therapeutic sensitivity and sur-vival. We identified a defect in DNA double strand break repair affecting both homolo-gous recombination and non-homologous end joining. Although HPV-positive cells were able to sense and respond to DNA damage, expression and recruitment of downstream re-pair proteins BRCA2 and DNA-PkCS was deficient. This defect correlated with increased sensitivity to PARP inhibitors in cell line and patient-derived xenografts. We then formed a second hypothesis that expression of DNA-PkCS is variable in the HPV-positive subtype which contributes to inconsistency in disease progression. Dif-ferential DNA-PkCS expression was confirmed in clinical samples. Interestingly, protein levels were inversely related to the abundance of HPV E6/E7 mRNA and trended to-wards significance as a predictor of disease recurrence. Lastly, in vitro knockdown of DNA-PkCS resulted in increased therapeutic sensitivity and decreased invasion in HNSCC cell lines. In HPV-negative HNSCCs, we hypothesized that activation of Notch signaling alters cell processes contributing to poor patient outcomes. We identified an association between activation of the Notch pathway and mortality in two independent data sets. High Notch activity correlated with increased expression of the pro-invasive gene FGF1. Notch activation also prompted an increase in cell migration and invasion which was de-pendent on FGF1 expression. Cell proliferation, cell cycle profile, and sensitivity to radi-ation were unaffected by Notch activity. These results indicate that DNA repair and Notch signaling are dysregulated in HNSCC, leading to variability in characteristics such as therapeutic sensitivity and tumor progression. Importantly, we determined that DNA-PkCS and FGF1 are markers of signal-ing activity which should be studied further as potential therapeutic targets in this disease.
Author: Saman Warnakulasuriya
Publisher: Springer
ISBN: 9402410848
Category : Medical
Languages : en
Pages : 285
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Book Description
This edited volume is about novel targeted therapies for the treatment of advanced neoplasms of the head and neck (HNSCC) with particular reference to oral squamous cell carcinomas and covers specific fields of cancer genetics and genomics for personalized medicine. The landmark studies from the HNSCC Cancer Genome Anatomy (TCGA) and the cancer Genome Atlas 2015 have revealed the multiplicity and diversity of genetic alterations in HNSCC. This remarkable body of information has elucidated novel druggable targets (eg. EGFR, mTOR, p53, survivin and aberrant microRNA) for therapeutic interventions in head and neck cancer. Readers will discover the importance of the biology and pathology of squamous cell carcinomas, the role of cancer stem cells and other factors that contribute to resistance to curative therapies such as hypoxia. We present an in-depth analysis of the HNSCC oncogenome describing the distinct molecular alterations in squamous cell carcinomas, which participate in specific molecular pathways whose dysregulation may contribute to most HNSCC cases. Final chapters of the book elucidate how these important cancer-driving molecular events and molecular pathways could be targeted to treat head and neck cancers and their therapeutic applications for targeted therapies based on clinical trials reported worldwide. This book is aimed at a broad audience, including scientists, physicians, surgeons, and post graduate students engaged in oncology and provide the readers with an up-to-date, interdisciplinary knowledge and tools to better understand the evolving areas of targeted gene therapy and the key concept of personalized medicine in head and neck cancer.
Author: Adam B. Glick
Publisher: Springer Science & Business Media
ISBN: 144197203X
Category : Medical
Languages : en
Pages : 471
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Book Description
Squamous epithelia form the lining surface of tissues in contact with the environment: the skin, oral mucosa, esophagus and respiratory tract, the genital tract, and several other specialized tissues. These tissues are at highest risk for exposure to environmental carcinogens such as UV, tobacco smoke and infectious agents. Cancers that form in squamous epithelia are among the most common human solid tumors and have high morbidity and mortality. These cancers include squamous cell carcinoma of the skin, oral cancer, head and neck and esophageal cancer, certain lung cancers and cervical cancer. We propose to organize the book so that the early chapters will focus on individual pathways and more specific mechanisms in both normal function and cancer, while the later chapters will be more integrative and include overviews of biomarkers and therapeutic development. This should increase interest for clinically oriented researchers. All authors will be encouraged to provide a balanced review in addition to highlighting their own work.
Author: Barbara Burtness
Publisher: Springer
ISBN: 3319787624
Category : Medical
Languages : en
Pages : 628
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Book Description
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.
Author:
Publisher:
ISBN: 9781441972040
Category :
Languages : en
Pages : 484
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Book Description
Author: Jan B. Vermorken
Publisher: Springer Nature
ISBN: 3030632342
Category : Medical
Languages : en
Pages : 363
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Book Description
This open access book discusses the most current issues in head and neck cancer with a focus on current trends such as biomarkers, precision medicine and immunotherapy. New approaches in the diagnosis such as liquid biopsies and imaging biomarkers to predict radiotherapy toxicity as well as approaches in the surgical management of head and neck cancers are discussed. The book discusses medical and surgical approaches in both primary, recurrent and metastatic disease and also covers approaches for rare head neck cancers. Readers will learn about the latest drug developments and epidemiological aspects in cancers ranging from Head and Neck Squamous Cell Cancer to Nasopharynx cancer. Edited by a team of world leaders in Head and Neck Cancer, this volume serves as an easy reference to the head and neck oncology practitioner and provides a contemporary overview for specialists the field. The chapters are based on the latest data presented at the 7th Trends in Head and Neck Oncology Conference and reflect the most up-to-date information in the field.
Author: Henning Bier
Publisher: Karger Medical and Scientific Publishers
ISBN: 3805577893
Category : Medical
Languages : en
Pages : 215
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Book Description
The development of head and neck cancer is a multistep process in which genetic as well as epigenetic alterations interfere with the regular functions of proto-oncogenes and tumor suppressor genes. In addition, carcinogenesis is promoted by the impairment of mechanisms responsible for the maintenance of genetic stability. The accumulation of crucial events such as evasion of apoptosis, lack of senescence, deregulated proliferation, invasion and metastasis, as well as neoangiogenesis eventually determines the malignant phenotype. The 16 articles of this volume span from advances in the understanding of underlying molecular pathways (conditional mouse model, folate activity, DNA repair, genomic heterogeneity, p53 family members, human papillomavirus), to preclinical and clinical studies investigating potential novel therapeutic targets (epidermal growth factor receptor, nuclear factor-kappaB, vascular endothelial growth factor, chemokine receptors, P53-based immunotherapy, virus-modified tumor vaccination), and biometric considerations on the evaluation of prognostic factors. This state-of-the-art publication is recommended reading not only for ENT specialists and oncologists, but also for molecular biologists and other subspecialists interested in head and neck cancer research.
Author: Rami El Assal
Publisher: Springer Nature
ISBN: 3030698521
Category : Medical
Languages : en
Pages : 233
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Book Description
Head and neck cancer (HNC) is a heterogeneous group of cancers that, if combined, represent one of the most common cancer types. Patients with HNC suffer significant morbidity and mortality due to the importance of the structures involved. Over two-thirds of these patients are diagnosed at a late stage, leading to a poor prognosis. Therefore, advancements in early detection and treatment of HNC are crucial. This second volume provides an up-to-date overview of the theoretical background in the field of head and neck cancer (HNC) as well as of the emerging research that is impacting our understanding of this disease. The book begins with a comprehensive review of the epidemiology, etiology, symptoms, diagnosis, and staging of HNC. Next, it covers the essentials of potentially malignant disorders of the oral cavity, an important variety of HNC. Subsequently, it covers the newly emerging research in the field of HNC. The overall goal is to shift towards precision medicine (discussed in detail in Volume I), which will bring individualized clinical benefit to patients with HNC. This second volume of Early Detection and Treatment of Head & Neck Cancers concludes with the topic of chronic pain associated with HNC, including both the mechanisms of pain and the management strategies, and the emerging oral mucoadhesive drug delivery approach for HNC. All HNC surgeons, scientists, residents, and individuals whose lives have been touched by this disease, will recognize the impact pain has upon a patient’s health and his or her recovery trajectory.
Author: Malay Chatterjee
Publisher: Springer Science & Business Media
ISBN: 1461407303
Category : Medical
Languages : en
Pages : 334
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Book Description
This book provides an overview of critical components of cell signaling machinery and its role in epithelial morphogenesis, proliferation, invasions and angiogenesis in human cancer and discusses novel types of protein kinase pathways.
Author:
Publisher: Elsevier
ISBN: 0443235473
Category : Science
Languages : en
Pages : 276
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Book Description
Targeting Signaling Pathways in Solid Tumors, Part A, Volume 385 in the International Review of Cell and Molecular Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on topics such as Drugging the Undruggable: Advances in Targeting KRAS Signaling in Solid Tumors, Emerging Trends in Gastrointestinal Cancers: Targeting Developmental Pathways in their Carcinogenesis and Tumor Progression, Importance of targeting various cell signaling pathways in solid cancers, Targeting signaling pathways in cancer stem cells: a potential approach for developing novel anticancer therapeutics, Factors affecting heterogeneity in breast cancer microenvironment: A narrative review, and much more. Additional sections cover Exploring TLR Signaling Pathways as Promising Targets in Cervical Cancer: The Road Less Travelled Provides the latest information on cancer research Offers outstanding and original reviews on a range of cancer research topics Serves as an indispensable reference for researchers and students alike
