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Recurrence and metastasis of malignancy is a multistep process that involves the escape of tumor cells from the primary location, systemic translocation in the body, and adaptation to the foreign microenvironment of distant sites. The spread of cancer cells is mediated by the interaction between tumor cells (seeds) and the microenvironment of the host organ (soil). Emerging evidence has revealed several stages of the invasion-metastasis cascade, including epithelial-mesenchymal transition, angiogenesis, and immune surveillance escape. Moreover, host organs could develop premetastatic niches and be more vulnerable to cancer cell colonization, adaptation and growth.
Metastatic disease is the most lethal aspect of human malignancies, making the understanding and continued research of the process of metastasis a crucial step in treating cancer. The proposed book, entitled “Experimental and Clinical Metastasis: A Comprehensive Review” aims to provide a clear and extensive review of the clinical and experimental implications of metastatic disease. This work focuses on recent contributions to the field of metastasis, and will highlight crucial findings in the molecular understanding of disseminated disease as well as standard and personalized medicine currently being investigated in the clinic. Topics will include, among many, gene properties of metastatic cells, molecular mechanisms of tumour growth and spread, animal models of metastasis, and clinical implications, markers and treatment for metastatic disease. With the participation of worldwide experts in the field of oncology, from major academic and government centres, this book will provide a leading manual for the study of the metastatic process, from benchside science to bedside care. In this light, the proposed book will facilitate classroom learning for both medical and graduate students, as well as serve as a tool for physicians and researchers interested in the metastatic process. In addition, this book will include the latest advances in basic science as well as leading technologies and theories of targeting metastatic cells. Most importantly, not only will basic and clinical aspects be discussed, but furthermore, the translational aspect of research in metastatic diseases will be emphasized.
This book covers the molecular and cellular aspects of cancer metastasis, and discusses the clinical aspect of micro- and macro-metastases, which result in the death of the majority of patients with cancer. The current edition attempts to examine the current status of the basic scientific and clinical research in the area, and is a very useful reference for clinicians, oncologists, and biologists. It is intended for undergraduates as well as postgraduates in the area of medicine, oncology, and cancer biology.
Targeted Therapy in Translational Cancer Research for the Translational Oncology series provides a comprehensive overview of recent developments in our understanding of tumor biology, elucidates the roles of targets and pathways involved in carcinogenesis, and describes current state-of-the-art anticancer therapy, as well as the most promising areas of translational research and targeted therapy. Introduces cutting-edge ‘bench to bedside and back’ breakthroughs which have transformed the diagnosis, prognosis, and treatment of cancer Covers basic principles of targeted therapy, including immunotherapy and the roles of cancer stem cells, the microenvironment, angiogenesis, epigenetics, microRNAs, and functional imaging in precision medicine Summarises major advances in therapeutic management of hematologic malignancies and solid tumors using conventional therapy, targeted therapy, immunotherapy, or novel treatment modalities
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.
Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites of metastasis is crucial for developing effective treatment strategies. Given the molecular heterogeneity of TNBC, the clinical success of new therapies additionally depends on the identification of reliable drug targets within each TNBC subtype for more effective patient stratification. The studies presented herein sought to address these matters, using clinically relevant patient-derived xenograft (PDX) models to characterize chemotherapeutic efficacy in distinct metastatic sites, to identify promising targeted therapeutic candidates and combination strategies, and to assess the translational potential of these therapeutic strategies, with a focus on both the basal-like and luminal androgen receptor (LAR) subtypes of TNBC. We hypothesized that therapeutic efficacy in the primary tumor setting would be maintained in the metastatic setting, and that PDXs of distinct TNBC subtypes would respond to particular targeted therapies based on the distinct molecular pathways that drive their progression. We therefore expected that therapies targeting the epidermal growth factor receptor (EGFR) and the androgen receptor (AR) would have efficacy in basal-like TNBC and LAR TNBC, respectively, and would be ideal for incorporation into novel combination regimens for these specific disease subtypes. Using a combination of in vitro and in vivo drug response studies, we identified a drug combination, co-targeting EGFR and survivin, that was synergistic across multiple PDX models of basal-like TNBC, despite some of these models responding differently to standard chemotherapies, thus revealing potential pathways that may serve as reliable drug targets in this subset of patients. Furthermore, we identified several potential drug targets and therapeutic candidates for combination with AR-targeted therapies in LAR TNBC. In addition to identifying novel therapeutic strategies that have potential to provide clinical benefit for these subsets of TNBC patients, these studies highlight the utility of PDX models for in vitro and in vivo drug development studies, and demonstrate that the molecular and drug response profiles of primary tumors are maintained in the metastatic setting, indicating that studies employing PDX mammary tumor models can be applicable in advanced disease. Collectively, the data generated in these studies have the potential not only to directly provide clinical benefit for TNBC patients, but also to inspire and inform countless future research endeavors seeking to improve the therapeutic landscape in breast cancer.
Continuous cell lines derived from human cancers are the most widely used resource in laboratory-based cancer research. The first 3 volumes of this series on Human Cell Culture are devoted to these cancer cell lines. The chapters in these first 3 volumes have a common aim. Their purpose is to address 3 questions of fundamental importance to the relevance of human cancer cell lines as model systems of each type of cancer: 1. Do the cell lines available accurately represent the clinical presentation? 2. Do the cell lines accurately represent the histopathology of the original tumors? 3. Do the cell lines accurately represent the molecular genetics of this type of cancer? The cancer cell lines available are derived, in most cases, from the more aggressive and advanced cancers. There are few cell lines derived from low grade organ-confined cancers. This gap can be filled with conditionally immortalized human cancer cell lines. We do not know why the success rate for establishing cell lines is so low for some types of cancer and so high for others. The histopathology of the tumor of origin and the extent to which the derived cell line retains the differentiated features of that tumor are critical. The concept that a single cell line derived from a tumor at a particular site is representative of tumors at that site is naïve and misleading.
Tumor Vascularization discusses the different types of growth of tumor blood vessels and their implications on research and healthcare. The book is divided into three parts: the first one, General Mechanisms, discusses different vessel growth mechanisms, such as sprouting angiogenesis, non-angiogenesis dependent growth, intussusceptive microvascular growth, vascular co-option and vasculogenic mimicry. The second and third parts, entitled Clinical Implications and Therapeutic Implications are dedicated to translating recent findings in this field to patient treatment and healthcare. This book is a valuable source for cancer researchers, oncologists, graduate students and members of the biomedical field who are interested in tumor progression and blood vessels. Explains new, non-orthodox concepts recently developed and related to the modality of growth of tumor blood vessels Provides information on the types of angiogenesis, non-angiogenesis dependent growth and vascular co-option, discussing both their similarities and differences Encompasses a discussion on clinical implications of tumor vascularization to translate research findings into treatment
The advances in drug delivery systems over recent years have resulted in a large number of novel delivery systems with the potential to revolutionize the treatment and prevention of diseases. Bio-Targets and Drug Delivery Approaches is an easy-to-read book for students, researchers and pharmaceutical scientists providing a comprehensive introduction to the principles of advanced drug delivery and targeting their current applications and potential future developments.
Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.