This volume reviews the current state of research on immune checkpoints and offers novel concepts. It discusses the two most important immune checkpoints: T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). It shows that antagonistic antibodies against these two molecules are highly effective in the treatment of various cancers and that PD-1 and CTLA-4 have been linked to the suppression of T-cell receptor signaling and co-stimulatory molecules. Further, the volume examines other agents, a number of cells, receptors and signaling molecules, that are also involved in the regulation of T-cell activation and extends the concept of immune checkpoints to "molecules and cells that negatively regulate T-cell activation". Playing essential roles in immune homeostasis, they could offer new targets for cancer immunotherapy, and for the therapy of autoimmune diseases. Written by internationally respected scientists, this book will appeal to basic scientists, clinicians, drug development researchers, and advanced students alike.

This book offers clear, accessible information on the causes of cancer and the multiple ways people can reduce their risk for this insidious disease. Like no other work, this much-needed volume gathers the latest research and understanding about the causes of cancer and methods of preventing the disease-and makes it all clear and accessible to the general reader. Cancer Causes and Controversies: Understanding Risk Reduction and Prevention describes common risk factors associated with particular types of cancer, including genetic predisposition, radiation and chemical carcinogens, diet, hormonal factors, infection, and smoking. The book then looks at the scientific evidence supporting the positive role of healthy nutrition, exercise, and diet in lowering cancer risk, as well as the dangers posed by a dysfunctional immune system compromised by chronic infection, unhealthy lifestyles, stress, and poor psychological health. Finally, the book provides an unbiased assessment of a number of controversies surrounding cancer causes and prevention, including screening and genetic testing, vitamin supplementation, genetically modified foods, chemical food additives, and cellular phones and deodorants as potential cancer-causing agents. Primary source materials derived from original scientific work including the National Resources for Molecular Biology (National Center for Biotechnology Information public database) and Cancer Research UK International scientific manuscripts and reviews in the field of cancer research from peer review journals Resources for more information on cancer (websites, association, centers, books)

In Hormone Therapy in Breast and Prostate Cancer, many of today's leading researchers and clinicians describe the principles underlying targeted hormonal treatments, assess the actions of new and established agents, and illustrate the new applications of hormonal chemoprevention for breast cancer. Topics range from preclinical and clinical antiestrogens to the inhibition of estrogen synthesis and the effects of androgen withdrawal. A wide variety of proven and new agents are discussed-antiestrogens, including aromatase inhibitors (anastrozole, letrozole, and others), SERMs (tamoxifen, raloxifene, and others), and such antiandrogenic strategies as goserelin and bicalutamide.

This book focuses on how obesity and sedentary lifestyles adversely affect cancer risk and survival for individuals as well as mechanisms that may underlie those associations. However, evidence is accumulating rapidly on the cost of obesity and sedentary lifestyles to society. For example, obesity is estimated to lead to costs of $147 billion in the US.6 While research on individual level interventions for weight loss and increasing physical activity have identified efficacious approaches, these changes in behavior are not maintained by many in the current environments in the US and worldwide that promote weight gain and inactivity. Research on environmental and policy approaches for addressing these problems at the societal level is needed7, 8 and is a major component of the President's Report on Childhood Obesity released in April 2010. The epidemic of overweight and obesity and the increasing sedentary lifestyles will impact the magnitude and quality of the cancer problem globally. Increasing the knowledge of scientists, clinicians, and policy experts will aid in defining new prevention and treatment methods, to reduce the impact of energy balance on cancer, with the goal to eventually reduce the burden of cancer. Hopefully, this knowledge can be translated into incentives for the general public, persons at high risk, and cancer patients and survivors to increase physical activity, reduce excess weight, and maintain energy balance lifelong.

This volume is based on the Workshop on Systems Biology of Tumor Dormancy meeting, held July 25th to July 28th, 2011. The first annual CCSB workshop brought together biologists, clinicians, mathematicians, and computer scientists to discuss various aspects of tumor dormancy and develop novel mathematical/computational models with the keynote speakers. Specific topics included the angiogenic switch, immune system interactions, cancer stem cells and signaling.

This book reviews recent breakthroughs in anti-cancer drug discovery. Building on the previous volume in the series, it outlines some of the most significant developments that have occurred in the field in the subsequent period that have led to new drug approvals or promising clinical candidates. The volume is divided into chapters that each relate to a specific protein or protein class. Each chapter provides an overview of the underlying biology and then emphasises the medicinal chemistry strategies and tactics that led to the most significant drugs and drug candidates. A summary of clinical data and the future outlook for the field is also provided. Each chapter is authored by experts in the topic and who have themselves made significant contributions to their respective fields.

Cancer and Pregnancy covers the clinical challenges to diagnosing and treating malignancies in the pregnant patient; however, the book also shows how an understanding of the common features of both processes (rapid cell proliferation) may lead to novel anti-cancer treatment options. The book should be read by obstetricians and gynaecologists, clinical oncologists, reproduction specialists, and those involved in investigation of development, biology, toxicology, immunology, as well as cancer research.

Where do you begin to look for a recent, authoritative article on the diagnosis or management of a particular malignancy? The few general oncology text books are generally out of date. Single papers in specialized journal are informative but seldom comprehensive; these are more often preliminary reports on a very limited number of patients. Certain general journals frequently publish good in-depth reviews of cancer topics, and published symposium lectures are often the best overviews available. Unfortunately, these reviews and supplements appear sporadically, and the reader can never be sure when a topic of special interest will be covered. Cancer Treatment and Research is a series of authoritative volumes that aim to meet this need. It is an attempt to establish a critical mass ofoncology literature covering virtually all oncology topics, revised frequently to keep the coverage up to date, and easily available on a single library shelfor by a single personal subscription. We have approached the problem in the following fashion: first, by dividing the oncology literature into specific subdivisions such as lung cancer, genitourinary cancer, pediatric oncology, etc.;and second, by asking eminent authorities in each of these areas to edit a volume on the specific topic on an annual or biannual basis. Each topic and tumor type is covered in a volume appearing frequently and predictably, discussing current diagnosis, staging, markers, all forms of treatment modalities, basic biology, and more."

This volume presents the most current reviews on how cancer stem cells (CSCs) hypothesis dictates that the continued proliferation of a tumor is dependent on a sub-population of self-renewing and asymmetrically dividing neoplastic stem cells that supply a largely differentiated tumor. This volume provides a comprehensive overview of the characteristics of CSCs, their role in central nervous system (CNS) tumors, and the recent CSC-specific treatment modalities being used. The emerging focus on CSCs in brain tumors represents a paradigm shift in our understanding of the pathogenesis of these neoplasms. Importantly, the realization that a distinct sub-population of cells contributes disproportionately to the growth and sustenance of central nervous system tumors has important implications for the treatment of such tumors. To treat CNS tumors, there is now a growing need to treat CSCs to achieve adequate tumor control.

Research over the past decades has firmly established the genetic basis of cancer. In particular, studies on animal tumour viruses and chromosome rearrangements in human tumours have concurred to identify so-called 'proto-oncogenes' and 'tumour suppressor genes', whose deregulation promotes carcinogenesis. These important findings not only explain the occurrence of certain hereditary tumours, but they also set the stage for the development of anti-cancer drugs that specifically target activated oncogenes. However, in spite of tremendous progress towards the elucidation of key signalling pathways involved in carcinogenesis, most cancers continue to elude currently available therapies. This stands as a reminder that "cancer" is an extraordinarily complex disease: although some cancers of the haematopoietic system show only a limited number of characteristic chromosomal aberrations, most solid tumours display a myriad of genetic changes and considerable genetic heterogeneity. This is thought to reflect a trait commonly referred to as 'genome instability', so that no two cancers are ever likely to display the exact same genetic alterations. Numerical and structural chromosome aberrations were recognised as a hallmark of human tumours for more than a century. Yet, the causes and consequences of these aberrations still remain to be fully understood. In particular, the question of how genome instability impacts on the development of human cancers continues to evoke intense debate.

This book is a logical companion volume to Women at High Risk to Breast Cancer (Kluwer, 1989) edited by me previously. It distinguishes two aspects of current ap proaches to clinical breast cancer prevention. The first is the need to advise individ ual women on how they might reduce their personal risk, while the second is the design of measures aimed at reducing the total incidence of breast cancer in the community. While the former is a problem faced daily by clinicians, the latter is a goal which will involve large scale, carefully planned interventional studies. Because knowledge of the risk factors for breast cancer is incomplete and clinical trial reports are scarce, there is as yet, no scientifically-based model for personal breast cancer prevention. Nevertheless, widespread publicity associated with breast screening programmes has created a large group of highly anxious women who have been informed that they are at higher than average risk to the disease. They are con cerned by the personal threat posed by a family history of the disease and by the al leged dangers of obesity, diet, alcohol, or the use of hormonal agents such as oral contraceptives or hormone replacement therapy."

The aim of Apoptosis and Cancer is to describe the performance of contemporary techniques for studying the biology of apoptosis and its role in cancer. The protocols described will aid both the academic laboratory interested in further characterizing the mechanisms of apoptosis, as well as the industry laboratory, aimed at identifying new target molecules or screening for new compounds with potential clinical use.

Proceedings of the 5th Biannual International Meeting on Angiogenesis: From the Molecular to Integrative Pharmacology, held July 1-7, 1999, in Crete, Greece. Angiogenesis, as a vastly complex biological process, has challenged researchers from all basic scientific disciplines, including pharmacology, biochemistry, physiology, embryology and anatomy. The significance of this phenomenon for the study of disease states has also interested clinicians from a number of specialist fields. This multidisciplinary work reflects the growth of awareness of concepts such as angiogenesis based therapy, the enormous therapeutic and commercial potential of which has attracted major research and investment in recent years. This volume, which aims to bridge the gap between basic and clinical methodology and understanding, presents the most up-to-date developments in this field.

This volume, with contributions from the most recognized experts in preventive strategies in breast cancer, presents the accepted as well as the novel ideas that have been introduced for the prevention of breast cancer. There is no single preventive agent that can stop the incidence of breast cancer-the malignant disease most frequently diagnosed in women of all races and nationalities. Furthermore, its incidence around the globe is increasing in industrialized countries. The worldwide incidence of breast cancer has increased 30-40% since the 1970s, reaching an excess of 1,390,000 new cases and a mortality of more than 460,000 cases in 2015. Therefore, what is needed is the development of rational strategies for the prevention of this fatal disease.

This volume emphasizes metastasis/dissemination as im nective tissues, muscle, tumours of neuronal origins and portant processes in cancer growth and progression. teratomas. Previous volumes in this series have emphasized aspects of The broad array of neoplastic diseases, multiple target cancer progression, tumor invasion and tumor metastasis sites, and patterns of metastasis and dissemination underlie and the importance of these processes to the pathophysiol the importance of achieving crucial insights into particular ogy and morbidity of malignant disease. This volume builds neoplasms. An understanding of metastasis and dissemina on these earlier themes and emphasizes metastasis/disse tion in man remains an essential objective for the design of mination in man. Following a review of general patterns of new diagnostic and therapeutic strategies for the therapy of metastatic spread in man, metastasis to, or progression of established metastatic disease and spread accompanying neoplasms in several organ systems are highlighted, includ site-specific tumor progression. ing: the central nervous system, esophageal cancer, the lung, the large intestine, the liver, bone, epithelial neoplasms, Series Editor Volume Editor endocrine cells, pigmented tissues, supporting tissues, con- Hans E. Kaiser Elizier L. Gorelik VII ACKNOWLEDGEMENT Inspiration and encouragement for this wide ranging project on cancer distribution and dissemination from a comparative biological and clinical point of view, was given by my late friend E. H. Krokowski.

Biomedical Science Chinese herbal medicine represents complementary or adjunctive therapies that often can improve the efficacy of Western medicine to achieve the pharmacological effects, especially in cancer treatment. However, the combination of herbs with therapeutic drugs can raise potential health risk. Building a bridge between Western medicine and herbal medicines, Active Phytochemicals from Chinese Herbal Medicines: Anti-Cancer Activities and Mechanisms gives you useful information on how integrated medicines can work for cancer therapy. It discusses the therapeutic uses of phytochemicals, adverse effects, and interactions with (Western) cancer drugs. The author takes a unique approach to integrated pharmacology of herbal medicines, examining the development of phytochemicals and their mechanisms of action in the context of the cancers and diseases they are used to treat. He covers biologic action of the active phytochemicals at the molecular, cellular, and organ levels. The book covers the principles of the interaction of phytochemicals and the related drug actions. It also addresses the common pathways affecting cancer development before discussing the phytochemical classes and specific phytochemicals that have been recently reported in journal papers for the management of cancer and other diseases. Highlighting the increasingly important aspects of pharmacology, including health benefit and drawbacks of phytochemicals, the book presents the relevant background of the biochemistry of the cancer. It includes illustrations and tables with adverse reactions that highlight important issues related to phytochemical actions. These features and more make the book a useful reference on phytochemicals obtained from herbal medicines. It blends coverage of fundamental mechanisms of anti-cancer action and the use of phytochemicals to manage cancers and other human diseases, allowing you to explore how herbal medicines can enhance conventional protocols.

This book represents an up-dated summary of the state of the art of the characterization of cancer stem cell/ cancer initiating cell (CSC/CIC) properties. An overview of the definition and biological properties of CSCs/CICs as well as the role of these cells in determining the resistance to standard and immune-based therapies is provided. It also discusses limitations in the achievement of a definitive biological characterization of CSCs/CICs due to their high extent of plasticity and heterogeneity that is also mutually driven by the interaction of these cells with the tumor microenvironment. The limitations in targeting CSCs/CICs with immunotherapy are also explained together with explorative combination approaches that could increase the susceptibility of these cells to the recognition by immune cells. This book is conceived for a broad audience, including students, teachers, scientific experts. The critical revision of available results in terms of immunological profile of CSCs/CICs and the efficacy in targeting these cells by immunological approaches, results in a comprehensive and up to date recapitulation of the field and provides interesting suggestions on how to focus future investigations in order to assess the role of CSCs/CICs as prognostic and predictive biomarkers of responsiveness to therapies for cancer patients.

Health has been conceptualized by world and national health organizations (WHO, CDC, Healthy People 2010) as more than the absence of disease. It involves a focus on physical, psychosocial, and functional aspects of life as well as the prevention of future illnesses. At this point in the development of quality health care for cancer survivors, there is sufficient knowledge and expert opinion to push efforts forward to improve the health of cancer survivors. Clearly there is more research in the most prevalent forms of cancers (e.g., breast cancer) than others that provide us with guidance on how to optimize their health, but there are data on other forms of cancers that can also better inform practice. There may also be general care practices that can cut across cancer types. There has been an emergence of epidemiological and clinical research in cancer survivors that can form the basis for a revolution in the quality and nature of health care that survivors receive. This book not only provides the reader with diverse perspectives and data but also integrates this information so it can serve as the foundation necessary to improve and maintain the health of cancer survivors. Reporting of symptoms to health care providers is a complex, multi-determined problem influenced not only by the pathophysiology but also, as we have learned over the years through pain research, by societal, cultural, and biobehavioral factors. This book will consider this important aspect of follow-up for millions of cancer survivors because of the strong reliance on symptom reporting for clinical decision making. In order for us to generate meaningful and effective treatment, we need to better understand the symptom experience in cancer survivors. This book provides much information that will assist us to better understand and manage this complicated end point. The presenting problems need to be articulated and "conceptualized" as clearly as possible by both parties so appropriate actions can be taken. Since health care costs are a major concern for patients, payers, and providers, this area will also be addressed in all the relevant sections. In taking an interdisciplinary perspective, this book illustrates the importance of a team approach to the improvement of health care and associated health, well-being, and functioning in cancer survivors. The 17 chapters cover critical topics of which physicians and providers of all types must be aware in order to provide the most comprehensive and responsive care for cancer survivors. All of the clinical care chapters include case studies to illustrate the real-world application of these approaches in cancer survivors. Information about sources of referral both within and outside the traditional health care communities will be provided in tabular form. There is no other text that provides both an overview of the problems and their challenges, case illustrations of direct application, and the reality of reimbursement for such care. The editors hope that there may be no need for the clinician or the survivor to adapt to a "new normal" if the presenting problems are understood and handled from an interdisciplinary perspective as outlined here.

The combination of molecular biology, engineering and bioinformatics has revolutionized our understanding of cancer revealing a tight correlation of the molecular characteristics of the primary tumor in terms of gene expression, structural alterations of the genome, epigenetics and mutations with its propensity to metastasize and to respond to therapy. It is not just one or a few genes, it is the complex alteration of the genome that determines cancer development and progression. Future management of cancer patients will therefore rely on thorough molecular analyses of each single case. Through this book, students, researchers and oncologists will obtain a comprehensive picture of what the first ten years of cancer genomics have revealed. Experts in the field describe, cancer by cancer, the progress made and its implications for diagnosis, prognosis and treatment of cancer. The deep impact on the clinics and the challenge for future translational research become evident.

Metastasis is the primary cause of mortality associated with cancer, and tumor genomic heterogeneity is a likely source for the cells that support cancer progression, resistance to therapy, and disease relapse. This book connects cancer metastasis with genomic instability in a comprehensive manner. Section 1 outlines the fundamental mechanisms responsible for these cellular and tissue phenotypes. Section 2 discusses in silico, in vitro, and in vivo models used for the experimental study of these processes. Section 3 reviews emerging themes (ex., microenvironment, mechanotransduction, and immunomodulation), and Section 4 highlights new therapeutic approaches to overcome the unique challenges presented by the heterogeneous and metastatic tumor. This book is intended for undergraduates and postgraduates with an interest in the areas of medicine, oncology, and cancer biology as well as for the content expert searching for thorough reviews of current knowledge in these areas.

The purpose of Diagnostic and Therapeutic Advances in Pediatric Oncology for the Cancer Treatment and Research Series is to provide an up-to-date summary of how recent advances in cancer research are being applied to the care of children with solid tumors. The interface of cancer research with clinical practice in pediatric oncology has never been more intimate than today. While researchers are identifying oncogenes and tumor suppressor genes and are studying their specific functions, clinicians are using knowledge of oncogenes and tumor suppressor genes for diagnosing cancer in children, for therapeutic decision-making purposes, and for prognostic purposes. The first three chapters in this book describe models for understanding the causes of childhood cancer that were perhaps initially identified by clinicians and that are now being studied and understood by researchers. These chapters will describe research evidence that supports roles for the involvement of normal developmental regulatory genes in childhood oncogenesis, of abnormal immune regulation in childhood oncogenesis, and of heredity in childhood oncogenesis. The next eight chapters are devoted to descriptions of the appli cation of new research developments to clinical practice with reference to the most common forms of solid tumors of childhood outside the central nervous system. The final chapter will describe late effects of childhood cancer and its therapy and the impact research is having on understanding and perhaps preventing these late effects.

In Leukemia and Lymphoma: Detection of Minimal Residual Disease, hands-on experts describe and discuss the minimal residual disease (MRD) methods they have successfully pioneered for leukemias and lymphomas. They apply reverse transcription PCR (RT-PCR) to acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), and acute promyelocytic leukemia (APL). Other PCR methods are used for Non-Hodgkin's Lymphoma and for the monitoring of follicular lymphoma. Additional chapters address the use of real-time quantitative PCR (RQ-PCR), the emergent method of choice, in patients with acute lymphoblastic leukemia (ALL), the evaluation of MRD techniques in clinical trials, and the application of flow cytometry techniques.

This volume reviews our current knowledge concerning can Several chapters discuss the contributions of genetic asp cer growth and progression as it relates to the etiology of ects, metabolism, endocrine-related aspects and nutrition to human cancer. As emphasized in Volumes I-V of this series, cancer progression. Moreover, our current knowledge con neoplastic diseases are multistep maladies. There are many cerning urbanization factors, radiation, therapy-induced causes for the appearance of neoplastic diseases. Earlier neoplasms, environmentally induced neoplasms (e. g., chapters in the series have reviewed molecular and cellular mesotheliomas induced by asbestos) and malignant neo aspects of tumor initiation, promotion and progression to plasms in organ transplant recipients are summarized. the invasive and metastatic phenotype. Contributions to the The impact of AIDS on neoplasm development is re initiation and progression of neoplastic diseases are made by viewed from an epidemiologic perspective that explores mul natural features of the environment and by its contaminants tiple facets of immunity, infectious disease, sexual behavior and by nutritional factors. Neoplastic diseases show a dis and blood transfusion. Other chapters investigate the in tinct relationship to a variety of environmental stimuli and fluence of the host immune response in oncogenesis and the to diseases of a non-neoplastic nature. For example, familial relationship between atherosclerotic plaques and tumors."

The present book is a collection of original contributions by specialists in fields related to the more advanced methods presently used or foreseen in the near future for cancer therapy. The use of larger nuclear installations, like particle accelerators and nuclear reactors in oncology is treated in detail, giving an interesting overview of their present and future potential. The aim of the book is to clarify the present state of the art and to encourage new interest in the many fields related to cancer research. The book is particularly suitable for people working in cancer research, but also in other fields, like particle accelerators, nuclear reactors, nuclear medicine and radio-pharmaceutical research. The methods presented in the book are sometimes tentative or not completely established, but clearly reveal the efforts being made to acquire new knowledge for the solution of one of the more serious problems involving the whole of mankind. The book is also required reading for those who want to be informed about the medical research work in large nuclear installations and the most advanced trends in nuclear medicine.

This book is a comprehensive review of the current knowledge on cytokines and cancer. Cytokines play a variety of roles in cancer, both as components of pathogenetic mechanisms, as well as agents used in the treatment of certain malignancies. To date, there has not been a book that covers both basic science and translational/clinical research in the field of cytokines in malignancies. This book is written by leading figures in the field of cytokine biology and cytokine therapeutics and is specifically focused on this subject. The book is divided into two parts. The first part is focused on current developments in the basic science field. There is a particular emphasis on novel mechanisms of cytokine actions in malignant cells. The second part deals with translational and clinical research in the field, and many of the authors of these chapters were among the first to introduce several cytokines in the treatment of certain tumors. Collectively, the information provided in this book will be helpful to people in the medical field at several levels, including medical students, interns, residents, clinical and basic science researchers, as well as oncologists in practice.