This book reviews the potential of next-generation sequencing (NGS) in research on and management of colorectal cancer (CRC), a leading cause of death worldwide and one of the most biologically and clinically heterogeneous cancers. It critically discusses findings from recent large-scale studies, clinical trials and meta-analyses and offers an introduction to the management of CRC in the era of precision medicine. In CRC, dozens of driver and passenger mutations are associated with the malignant transformation of epithelial cells. Consequently, the book discusses recent advances in our understanding of the genetics of CRC as a biomarker, the advent of NGS technologies in modern genomics, and the impact of NGS technology on the management of CRC. Furthermore, it highlights the potential of NGS in the context of liquid biopsy and single-cell sequencing in CRC, as well as its role in shedding light on the link between gut microbiota, immune-checkpoint blockade and CRC. The book concludes with a chapter on the limitations and cost-effectiveness of NGS in CRC. Given its scope, the book will appeal to all those interested in learning about the potential of NGS in advancing CRC research and patient care.

The tiny microRNAs (miRNAs) can have huge impacts on the regulation of a variety of genes and play crucial roles in the fundamental cellular processes. Recent miRNA studies change the landscape of cancer genetics by scrutinizing the alterations of genome-wide miRNA expressions in most common cancers and their regulatory functions during the development of cancer. The connections between miRNAs and cancer are widespread enough to warrant more comprehensive investigations in the systems biology perspective. In MicroRNA and Cancer: Methods and Protocols, internationally renowned experts provide the latest miRNA knowledge, the various techniques and methodologies currently available for cancer research application. Ranging from the fundamental concepts to practical applications, this book presents: * Overview of microRNA biogenesis, computational prediction of new miRNAs in the cancer genome, and miRNA-based therapeutic approaches for cancer treatment * Detailed experimental protocols in miRNA detection with novel and high-throughput technology, miRNA library cloning, miRNA epigenetic regulation, and miRNA pathway study * Stepwise computational and bioinformatic procedures for miRNA complex networks in cancer genomes with a variety of softwares and programs * Cross-cited notes on troubleshooting and avoiding known pitfalls Authoritative and cutting-edge, MicroRNA and Cancer: Methods and Protocols serves researchers with the basic principles of experimental and computational methods for microRNA study in cancer research and provides a firm grounding for those who wish to further develop their own applications and tailor them to their own specific research needs.

Patients with advanced breast or prostate cancers usually develop bone metastases. The principal complications resulting from metastatic bone disease are pain, spinal cord compression, pathologic fractures and bone marrow suppression. Improving the management of bone metastases is crucial to quality of life for patients with breast and prostate cancer.

Advances in understanding of the molecular mechanisms underlying the pathophysiology of bone metastasis are driving the development of new therapeutic strategies.

It has become clear that tumors result from excessive cell proliferation and a corresponding reduction in cell death caused by the successive accumulation of mutations in key regulatory target genes over time. During the 1980s, a number of oncogenes were characterized, whereas from the 1990s to the present, the emp- sis has shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and TSGs function in the same pathways, providing positive and negative growth regulatory activities. The signaling pathways controlled by these genes involve virtually every process in cell biology, including nuclear events, cell cycle, cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Mu- tions in tumor suppressor genes have been identified in familial cancer syndromes, and the same genes in many cases have been found to be mutationally inactivated in sporadically occurring cancers. In their normal state, TSGs control cancer development and progression, as well as contribute to the sensitivity of cancers to a variety of therapeutics. Understanding the classes of TSGs, the biochemical pa- ways they function in, and how they are regulated provides an essential lesson in cancer biology. We cannot hope to advance our current knowledge and to develop new and more effective therapies without understanding the relevant pathways and how they influence the present approaches to therapy. Moreover, it is important to be able to access not only the powerful tools now available to discover these genes, but also their links to cell biology and growth control.

Over the years of cancer investigation a lot of discoveries in this field were made, and many associations between various biological carcinogens and cancer were revealed. Some of them are credibly determined, thus these infectious agents (human papilloma virus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, human herpes virus 8, human T-cell lymphotropic virus 1, human immunodeficiency virus, Merkel cell polyomavirus, Helicobacter pylori, Opisthorchis viverrini, Clonorchis sinensis, Schistosoma haematobium) are recognized as carcinogens and probable carcinogens by International Agency for Research on Cancer (IARC). The problem is of large importance, since share of infectious agents-related cancer cases is steadily increasing, reaching 25% according to certain estimates. It is worth noting that many of cancer cases are caused by infectious agents other than -conventional ones- like HPV, EBV, HBV, HCV, H.pylori etc. In recent years, a number of significant breakthroughs in the field were performed, such as the discovery of the microbiota role in cancer causation."

From humble beginnings over 25 years ago as a lipid kinase activity associated with certain oncoproteins, PI3K (phosphoinositide 3-kinase) has been catapulted to the forefront of drug development in cancer, immunity and thrombosis, with the first clinical trials of PI3K pathway inhibitors now in progress. Here we give a brief overview of some key discoveries in the PI3K area and their impact, and include thoughts on the current state of the field, and where it could go from here

The concomitance of cancer and pregnancy is a biological paradox and one of the greatest challenges in the lives of young patients, their partners, and their families. It is also a challenge to oncologists, because the management of the pregnant cancer patient involves both mother and fetus. Ideally, oncologists, reproductive endocrinologists, obstetricians and neonatologists, nurses, and psychologists work within a dedicated multidisciplinary team to deliver optimal cancer therapy to the mother, while assuring fetal well-being.

This book, written by oncology experts with knowledge and clinical expertise on diagnosis, treatment, and follow-up of women with different types of cancer during pregnancy, provides a comprehensive review of existing data on cancer during pregnancy and a general overview of its psychological, ethical, and social aspects. Chapters address the diagnosis, treatment, and follow-up of young women with specific solid or hematologic cancers during pregnancy. The safety of subsequent pregnancy after cancer treatments and the alternatives to maintain or enhance fertility in women undergoing cancer therapy are also addressed. While not intended as a practical guideline, the book contains clinical suggestions, bibliography, and references to available online sources about referral centers, ongoing clinical trials, and tumor registries to help oncologists in the clinic.

This work presents the most advanced discoveries from translational research laboratories directly involved in identifying molecules and signalling pathways that play an instrumental role in metastasis. In contrast to other works, conventionally focused on a single type of tumour, the various chapters in this book provide a broad perspective of the similarities and discrepancies among the dissemination of several solid malignancies. Through recurrent and overlapping references to molecular mechanisms and mediators, the readers will gain knowledge of the common ground in metastasis from a single source. Finally, an introductory chapter provides a clinical perspective of the problems presented by metastatic tumours for diagnosis and treatment. The work presented here is directed to researchers in tumour biology with a developing interest in metastatic dissemination as well as medical and graduate students seeking to expand and integrate the notions acquired in basic cancer biology and oncology courses.

During the last 20 years it has become increasingly clear that the tumor micro-environment, the tumor stroma with its cellular end extracellular components, plays an crucial role in regulating tumor growth and progression. This book on "Tumor-associated fibroblasts and their matrix" as part of the series on "Tumor-Microenvironment" is the first comprehensive discussion of these two main players of the tumor microenvironment. The best experts in this new area of tumor research and therapy review the role of these major components in the tumor stroma in the process of tumor development and progression. They discuss their interaction with other players such as blood vessels and immune cells, and show novel perspectives for tumor therapy. This compilation of excellent contributions of the best known experts in this important field in cancer research and therapy is a must for all scientists engaged in basic and clinical research. Increasing evidence of successful targeting of both cellular and matrix components in tumor therapy renders this book of particular interest for scientists engaged in pharmaceutical industry searching for new components for cancer therapy.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. CLL has a highly varied clinical course. While advances in CLL therapy are noted, many patients still succumb to this illness. Like most progress in medicine, solid advances in the diagnosis, prognosis and treatment of CLL are rooted in an in-depth understanding of the basic and translational biology of CLL. In this book, CLL experts have contributed state-of-the-art summaries of various important aspects of CLL biology and have discussed the translational implication of such findings. This book, which is directed at physicians and researchers alike, aims to educate broadly and deeply. Intentionally, the many aspects and nuances of CLL clinical care that can only really be appreciated through direct patient care are not covered here, but instead, the book presents basic aspects of CLL that underlie many of the contemporary decisions that are made in CLL research and clinical settings.
We hope that this book will critically inform the community and stimulate interest in CLL, which will ultimately translate into better CLL research, prognostication and therapy, with the end goal of providing a better outlook for patients afflicted with this common leukemia."

Hematopathology: Genomic Mechanisms of Neoplastic Diseases will keep physicians abreast of the rapid and complex changes in genomic medicine, as exemplified by the molecular pathology of hematologic malignancies. This timely volume will update physicians on the complexities of genomic lesions, as well as offer an integrated framework encompassing molecular diagnosis, the new WHO classification of hematologic neoplasms with focus on molecular pathology, prognostic value of molecular tests, and molecular monitoring of response to gene-targeted therapy. As such, it will be of great value to hematologists, oncologists, pathologists, internal medicine and pediatric specialists, as well as bioscientific staff and laboratorians in private hospitals and academic institutions.

The field of microRNA biology is really emerging in the last couple of years. Several investigators highlighted the importance of miRNAs in cancer. Although there is so much literature on microRNAs exist, a comprehensive book is still not available. Thus this book will be a great use to the scientists in the field of cancer biology. In addition, this book will be a good source of information for undergraduate, graduate students who want to develop their research careers in cancer biology.

Gene expression studies have revealed diagnostic profiles and upregulation of specific pathways in many solid tumors. The explosion of new information in gene expression profiling could potentially lead to the development of tailored treatments in many solid tumors. In addition many studies are ongoing to validate these signatures also in predicting response to hormonal, chemotherapeutic and targeted agents in breast cancer as well as in other tumors. Diagnostic, Prognostic and Therapeutic Value of Gene Signatures provides readers a useful and comprehensive resource about the range of applications of microarray technology in oncological diseases. Topics covered include gene signatures and soft tissue sarcomas, prognostic relevance of breast cancer signatures, gene expression profiling of colorectal cancer and liver metastasis, gene signatures in GISTs, CNVs and gene expression profiles in pancreatic cancer, and gene signatures in head/neck, lung and gastric tumors. Diagnostic, Prognostic and Therapeutic Value of Gene Signatures will be of great value to residents and fellows, physicians, pathologists and medical oncologists.

Leading investigators and clinicians detail the different mechanisms used by tumors to escape and impair the immune system and then spell out possible clinical strategies to prevent or reverse tumor-induced immune dysfunction. The authors review the mechanisms of immune dysfunction and evasion mechanisms in histologically diverse human tumors, focusing on tumor-induced molecular defects in T cells and antigen-presenting cells (dendritic cells and tumors), that may serve as biomarkers for patient prognosis. They discuss the means by which these immune functions may be protected or restored in order to more effectively support the process of tumor rejection in situ. Cutting-edge techniques are outlined with the capacity to monitor the strength and quality of patients' immune responses using immunocytometry, MHC-peptide tetramers combined with apoptosis assay, ELISPOT assay, and detection of MHC-TAA peptide complexes on tumor cells.

Genetic susceptibility refers to how variations in a person 's genes increase or decrease his or her susceptibility to environmental factors, such as chemicals, radiation and lifestyle (diet and smoking). This volume will explore the latest findings in the area of genetic susceptibility to gastrointestinal cancers, focusing on molecular epidemiology, DNA repair, and gene-environment interactions to identify factors that affect the incidence of GI cancers. Topics will include germline susceptibility, including Mendelian patterns of inheritance and gene-environment interactions that lead to cancer etiology.

This volume is a valuable and timely resource for a broad audience with interests in basic and translational cancer biology, cancer drug development, as well as in the practice of personalized oncology. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Cancer Gene Networks aims to ensure successful results in the further study of this evolving and vital field. Ultimately these efforts will guide development of transformative strategies for cancer diagnosis and treatment.

This comprehensive text provides a much-needed review of a disease that is currently garnering the interest of molecular biologists, translational scientists, and clinicians. The volume includes emerging developments in the molecular genetics of endometrial carcinoma. In addition to covering the basic genetics of endometrial carcinoma, chapters also cover a wide range of signaling pathways implicated in endometrial carcinoma. A section of the book includes a number of genetically engineered mouse models, which contribute to understanding the role of various genetic alterations in the development and progression of endometrial carcinoma. These models also provide preclinical models for developing effective targeted therapeutic approaches. Endometrial carcinoma is the most common malignancy of the female genital tract in the United States and the number of cases continues to increase around the world. This book is a meant to serve as a resource for a wide range of scientists, from molecular geneticists to signal transduction biologists, as well as to both clinicians and scientists interested in developing targeted therapeutic approaches for women with endometrial carcinoma.

This volume will detail the current state and perspectives of autophagy-based cancer therapy. Covering a wide range of topics, it will include an overview of autophagy as a therapeutic target in cancer, autophagy modulators as cancer therapeutic agents, implications of micro-RNA-regulated autophagy in cancer therapy, modulation of autophagy through targeting PI3 kinase in cancer therapy, targeting autophagy in cancer stem cells, and roles of autophagy in cancer immunotherapy. In addition, the volume will review applications of system biology and bioinformatics approaches to discovering cancer therapeutic targets in the autophagy regulatory network. The volume will be beneficial for a variety of basic and clinical scientists, including cancer biologists, autophagy researchers, pharmacologists, and clinical oncologists who wish to delve more deeply into this field of cancer research. This volume will be the first book to focus solely on autophagy as a target in cancer therapy. As well, it will comprehensively discuss the roles of autophagy in most currently available cancer treatments.

This volume details basic principles of experimental and computational methods for the study of microRNAs in cancer research and, therefore, provides a firm grounding for those who wish to develop further applications. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, MicroRNA and Cancer: Methods and Protocols, Second Edition aims to ensure successful results in the further study of this vital field

This book discusses the recent developments in the therapeutic implications of cancer stem cells for the effective diagnosis, prognosis, and treatment of cancer. It summarizes the various stem cells of common cancers including colon, pancreas, lungs, prostate, melanoma, and glioblastoma, and reviews the potential role of cancer stem cells in tissue aggressiveness, examining the functional contribution of cancer stem cells in the establishment and recurrence of cancerous tumors. Further, it explores the potential of cancer stem cells as novel therapeutic targets for the treatment and prevention of tumor progression. The book also discusses the various approaches for detecting, isolating, and characterizing different cancer stem cells and signaling pathways that control their replication, survival, and differentiation. Lastly, it explores the key features and mechanisms of drug resistance, chemo-resistance, and radio-resistance in cancer stem cells to improve therapeutic rationale.

This volume provides a biological and pharmacological background for regional cancer therapy, strategies and techniques for regional therapies, and specific indications and results for different tumor entities. Clinical trial concepts and detailed treatment protocols are also presented. This book is essential reading for researchers and clinicians engaged in seeking advanced therapeutic options for cancer patients worldwide.

The majority of cancers present at a relatively advanced stage in which invasion within the primary organ is well established and metastases to lymph and distant organs are either clinically apparent or present at the microscopic level. However, it is increasingly recognized that the natural history of cancer formation is a long and complex path taking many years to develop to a clinically apparent stage in most cases. Furthermore, for most solid tumours there is a pre-invasive or intraepithelial stage of disease. This affords the opportunity for early detection and prevention of invasive disease and hence a cure. However, with this advancing knowledge comes a whole plethora of questions which will be explored in this monograph. Firstly, we need to understand the global burden of pre-invasive disease and what the public health implications might be for wide-scale screening programmes. In the western world we already have experience of screening for cervical, breast, prostate and more recently colon cancer. As well as their potential benefits these programmes have financial and psychosocial implications which need to be carefully weighed. This is especially true since many pre-invasive lesions will not progress to cancer in a individual's lifetime. In addition, there are questions concerning whether screening reduces the cancer burden or in fact distorts the survival figures through lead-time bias. Secondly, at the level of epidemiology and molecular pathogenesis there are important questions regarding the aetiology of pre-invasive lesions; an understanding of which might lead to possible chemopreventive strategies. For example, it would be helpful to know the extent to which the likelihood of developing a pre-invasive lesion is influenced by lifestyle or genetic factors and how these factors influence the risk of progression to invasive disease. At the molecular level we need to understand the pathways and molecular mechanisms, both genetic and epigenetic, by which cells achieve the capacity to invade. Thirdly, in order make clinical progress we need biomarkers to identify and risk stratify individuals with pre-invasive lesions. These biomarkers might be applied to the serum as in Prostate Specific Antigen in prostate cancer or be applied to tissue samples, such as oestrogen receptor status in breast cancer. In order to utilize biomarkers in the context of a screening programme there are issue around the invasiveness of the test as well as its positive and negative predictive value. With advances in molecular imaging there is now the exciting possibility of incorporating a molecular tag to a non-invasive imaging modality. Fourthly, in order to justify screening early detection must be coupled to a treatment strategy. If the chemopreventive agent is very well tolerated, then as well as targeting high risk groups, one might consider treatment at the population level. Aspirin is one such drug which has been extensively assessed in the context of colon cancer chemoprevention trials. Trials of aspirin chemoprevention are now being applied to other cancers such as oesophageal adenocarcinoma and since many individuals take aspirin for .chemoprevention of cardiovascular disease the cancer incidence can be ascertained in these populations. In order to understand the more general issues raised from the discussions above it is useful to consider disease specific examples. Our understanding of pre-invasive disease varies according to the organ site and there are lessons to be learned from these experiences. For example, there is now the prospect of a vaccine for cervical cancer with important questions about how this might be applied to the high incidence areas of the developing world. On the other hand, ductal carcinoma in situ is currently treated by mastectomy which is more radical than the treatment received by many women with invasive disease. Oesophageal adenocarcinoma, which is my own area of expertise is interesting because of the rapid rise in incidence in the western world and the clinically accessible pre-invasive lesion called Barrett's oesophagus. However, most cases of Barrett's oesophagus remain undiagnosed and it is not yet clear how to effectively diagnose, monitor and treat this condition without recourse to mass endoscopy with substantial cost implications. In conclusion, in an era in which preventive medicine is a major concern for consumers, health-policy makers and politicians pre-invasive disease is likely to become a major part of cancer medicine.

Integrative medicine strives to incorporate the best of complementary and conventional modalities. This book details integrative oncology, a nascent field building a rigorous evidenced-based clinical medicine, research, and educational foundation. It examines five prestigious, comprehensive cancer centers based in the US, covering how these centers started their programs, what they are currently doing, and recommendations for starting integrative medicine clinics. The book also discusses the potential harm of alternative and complementary medicine, legal issues, and how to communicate with patients.

Nuclear receptors are ligand activated transcription factors that control numerous biological functions. Consequently, altering activity of these receptors is proposed, and indeed documented, to affect many physiological and pathological conditions in experimental animals and humans. Thus, nuclear receptors have become a major target in the effort to treat numerous diseases.This book will shed light on and emphasize intricate processes involved in designing as well as discovering physiological and pharmacological modulators of these important proteins. World-renowned scientists will share with the reader their professional expertise and extensive experience acquired through decades working with nuclear receptors. Chapters address the various means and consequences of modulating nuclear receptor activity will be presented and discussed. These modulators cover a wide span of moieties ranging from synthetic chemicals to natural products. In addition, the classification of these chemicals ranges from pan agonists to selective agonists and inverse agonists to antagonists. They also include proteolytic means to obliterate the receptor in the event that modulating its activity through canonical pharmacological agents becomes less effective and/or less desirable due to anticipated or experienced toxicities. Modulation of receptor activity may also take place in the absence of a ligand or through manipulating the structure of the receptor itself by controlling posttranslational events.