| 书目名称 | Circulating Tumor Cells | | 编辑 | Richard J. Cote,Ram H. Datar | | 视频video | http://file.papertrans.cn/227/226644/226644.mp4 | | 概述 | Provides a blueprint on how circulating tumor cells can be employed in the future.Features authors from diverse backgrounds in biology, biochemistry, and medical oncology?.Delivers a “one-stop” text t | | 丛书名称 | Current Cancer Research | | 图书封面 |  | | 描述 | This volume provides the latest research on circulating tumor cells aimed for cancer researchers, scientists, and molecular oncologists. It presents the basic concepts behind circulating tumor cells (CTCs), metastatic biology, and potential applications as to how CTCs can be used in diagnostic biomarkers..CTCs are cells that have detached from the primary tumor and circulate in the bloodstream. Such cells may become "seeds" for the growth of additional tumors. The field of analysis surrounding cancer metastasis has been steadily growing, and CTCs provide effective biomarkers that can be examined in peripheral blood through a minimally invasive “liquid biopsy” procedure. CTCs offer several exciting applications, not only as markers of disease progression but also as biomarkers of monitoring response to therapy and companion diagnostics for novel anticancer drug development. In recent years there has been rapid growth and worldwide developments on CTCs, which span both the basic sciences and biomedical engineering fields.. | | 出版日期 | Book 20161st edition | | 关键词 | biomarker; cancer; ctc; metastasis; tumor | | 版次 | 1 | | doi | https://doi.org/10.1007/978-1-4939-3363-1 | | isbn_softcover | 978-1-4939-8031-4 | | isbn_ebook | 978-1-4939-3363-1Series ISSN 2199-2584 Series E-ISSN 2199-2592 | | issn_series | 2199-2584 | | copyright | Springer Science+Business Media, LLC, part of Springer Nature 2016 |
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Front Matter |
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Abstract
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Abstract
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Significance of Studying Circulating Tumor Cells |
Ram H. Datar M.Phil., Ph.D.,Zheng Ao Ph.D.,Richard J. Cote M.D., F.R.C.Path., F.C.A.P. |
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Abstract
Circulating Tumor Cells (CTC) are tumor cells released into blood. They are considered the pivotal component of the metastatic cascade and are being extensively studied only in the last decade or so. Understanding the biological and clinical impact of CTC is likely to reveal important information of the metastatic process and contribute to better management of cancer. We briefly discuss here the current clinical utility of CTC and their emerging clinical applications.
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Affinity-Based Enrichment of Circulating Tumor Cells |
Zheng Ao Ph.D.,Richard J. Cote M.D., F.R.C.Path., F.C.A.P.,Ram H. Datar M.Phil., Ph.D. |
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Abstract
Study of CTC in cancer has always been hampered by its rare existence in blood. In this chapter, we discuss one of first principles employed to capture CTC from cancer patients’ peripheral blood—the affinity-based enrichment of CTC. We briefly discuss the different technologies utilizing antibodies to capture CTC based on specific antigen expression. Then we address the downstream molecular and functional characterization of CTC by utilizing these technologies. We also discuss the limitations of affinity-based CTC enrichment.
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Size-Based and Non-Affinity Based Microfluidic Devices for Circulating Tumor Cell Enrichment and Cha |
Zheng Ao Ph.D.,Kamran Moradi Ph.D.,Richard J. Cote M.D., F.R.C.Path., F.C.A.P.,Ram H. Datar M.Phil., |
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Abstract
Circulating Tumor Cells (CTCs) are tumor cells found in cancer patients’ peripheral blood. Enumeration of CTCs can provide prognosis information for cancer management (Cristofanilli et al., N Engl J Med 351(8):781–791, 2004; Cohen et al., J Clin Oncol 26(19):3213–3221, 2008; de Bono et al., Clin Cancer Res, 14(19):6302–6309, 2008; Poveda et al., Gynecol Oncol, 122(3):567–572, 2011). However, the technical hurdle for studying CTCs is their rare presence in blood, thus, isolating them is a non-trivial task. Two major categories of technologies have been developed in the past to isolate CTCs based on their biological expression of antigens (affinity-based capture) or based on their physical properties (non-affinity based capture). This chapter dedicates itself to the non-affinity based method for CTC capture. CTCs, as tumor cells, are inherently distinct from normal blood components. The chapter touches on the how these differences are reflected in their gene expression profiles, as well as their physical properties. We discuss how researchers utilized the unique biomechanical and electrical properties of CTCs to isolate them from enormous numbers of erythrocytes and leukocytes presen
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Molecular Assays for the Detection and Molecular Characterization of CTCs |
Evi S. Lianidou Ph.D.,Athina Markou Ph.D.,Areti Strati Ph.D. |
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Abstract
Detection of Circulating Tumor Cells (CTC) in peripheral blood can serve as a “liquid biopsy” approach and has thus emerged lately as one of the hottest fields in cancer research. A variety of molecular assays are continuously been developed for CTC detection and molecular characterization. Molecular assays are based on the nucleic acid analysis in CTCs like RT-qPCR, multiplex RT-qPCR, methylation specific PCR, ARMS-PCR, and next-generation sequencing technologies. The main strategies are based on total RNA isolation and subsequent mRNA quantification of specific genes, and isolation of genomic DNA for DNA methylation studies and mutation analysis. Molecular characterization of CTC holds considerable promise for the identification of therapeutic targets and resistance mechanisms in CTCs as well as for the stratification of patients and real-time monitoring of systemic therapies. Quality control and standardization of these methodologies is very important for the incorporation of CTCs into prospective clinical trials testing their clinical utility. This review is mainly focused on the basic principles and clinical applications of molecular assays that are currently used for the dete
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Cancer Stem Cells and Circulating Tumor Cells: Molecular Markers, Isolation Techniques, and Clinical |
Ebrahim Azizi Pharm.D, Ph.D.,Sunitha Nagrath Ph.D.,Molly Kozminsky M.S.E.,Max S. Wicha M.D. |
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Abstract
There is now a considerable body of evidence that many cancers are hierarchically organized and driven by a cellular component termed “cancer stem cells” (CSCs). These cells have the ability to self-renew and to generate heterogeneous populations that constitute the tumor bulk. Preclinical studies have demonstrated that CSCs mediate tumor metastasis and resistance to chemotherapy and radiation therapy. CSC biomarkers have been identified and both in vitro and mouse models have been developed to facilitate the isolation of these cells as well as the elucidation of CSC regulatory pathways. Agents targeting CSCs have now entered early phase clinical trials. The development of these clinical trials highlights the important need to develop technologies to monitor CSCs in patients. Unlike hematologic malignancies, where tumor specimens are readily obtainable, in solid tumors obtaining serial biopsies to assess CSCs is difficult. Studies suggest that circulating tumor cells (CTCs) contain a highly enriched proportion of CSCs and thus monitoring these cells in blood may provide a . for CSC assessment in solid tumors. In parallel with developments of efficient CTC isolation technologies, as
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Circulating Tumor Cells and Tumor Dormancy |
Alison L. Allan Ph.D.,Ann F. Chambers Ph.D. |
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Abstract
Metastatic cancer can recur months or even years after apparently successful treatment of the primary tumor. While the exact mechanisms leading to cancer recurrence remain poorly understood, failure to completely eliminate dormant micrometastases and solitary metastatic cells is believed to be a major contributor. Thus, while not of initial clinical concern, metastatic dormancy is still a significant clinical problem. The emerging use of circulating tumor cells (CTCs) as prognostic and predictive biomarkers for monitoring and understanding metastatic disease may provide an opportunity to address this challenge. In this chapter we discuss the current knowledge relating to CTCs and tumor dormancy, and the relationship between the two with regard to metastasis biology and treatment. We also consider the clinical impact of monitoring for CTCs in the absence of symptomatic tumor recurrence and what is needed for such an approach to providing “actionable” information that will improve patient outcome.
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Prevention of Conversion of Tumor Dormancy into Proliferative Metastases |
Dalit Barkan Ph.D.,Ann F. Chambers Ph.D. |
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Abstract
Late recurrences of cancer are believed to be due to dormant disease that can persist for long periods following apparently successful treatment of a primary tumor. Clinical tumor dormancy thus creates uncertainty for cancer patients and their physicians, who cannot be certain that their cancer will not recur. We have a poor understanding about which individual patients are at risk for cancer recurrence following a period of tumor dormancy. Thus, in spite of the clinical importance of tumor dormancy, much remains to be learned about the mechanisms responsible for induction of, and release from, dormancy. Here we consider the clinical problem of tumor dormancy and discuss evolving ideas of how tumor dormancy and reinitiation of growth may be regulated, both naturally in the body and therapeutically. A better understanding of mechanisms by which dormancy can be regulated may suggest new therapeutic approaches to either eliminate dormant cancer cells or promote the maintenance of dormancy.
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Genesis of Circulating Tumor Cells Through Epithelial–Mesenchymal Transition as a Mechanism for Dist |
Bee Luan Khoo M.Sc.,Prashant Kumar Ph.D.,Chwee Teck Lim Ph.D.,Jean Paul Thiery Ph.D. |
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Abstract
Epithelial–mesenchymal transition (EMT), a developmental process through which epithelial cells lose their characteristic apicobasal polarity and acquire the morphology of solitary migratory cells, has been implicated in the progression of carcinoma. EMT may contribute to the formation of cancer stem cells, evasion of immune surveillance, and induction of resistance to chemotherapeutics and targeted therapeutics. Metastasis is governed by a complex set of processes that are far from being fully understood and difficult to recapitulate through the current suite of in vitro experimentations. Circulating tumor cells (CTCs) in the peripheral blood have received much attention recently, as they may represent the first critical stage of cancer dissemination and their prevalence in metastatic patients is associated with worse prognosis. CTCs exhibit significant phenotypic heterogeneity across the EMT spectrum and preliminary studies have prompted the need to unravel the mechanisms by which CTCs are generated and how this diversity is attained in primary tumors. As such, improved methodologies are required to exhaustively characterize the full spectrum of CTC phenotypes and to identify the
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CTC Analysis: FISH, ISH, Array-CGH, and Other Molecular Assays |
Verena Tiran B.Sc., M.Sc.,Marija Balic M.D., Ph.D.,Nadia Dandachi Ph.D. |
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Abstract
Recent findings have unveiled a remarkable heterogeneity and complexity behind cancer diseases. Specifically, intratumoral heterogeneity has been associated with therapeutic failure and drug resistance, posing considerable clinical challenges to finding effective treatment modalities. Therefore, assessing tumor heterogeneity is clinically important for developing novel and efficient targeted therapy concepts. Molecular analysis of circulating tumor cells (CTCs) may be an exciting and promising surrogate biomarker to assess tumor heterogeneity. With recent advances in molecular analysis, single-cell profiling is possible and allows assessment of the extent of heterogeneity between individual cells. Molecular profiling of CTCs may help to identify specific subsets of CTCs with tumorigenic potential and paves the way for developing therapies specifically targeting these cells. Here we focus on currently used molecular assays, including (fluorescence) in situ hybridization, array-CGH, next-generation sequencing, qualitative and quantitative RT-PCR, and microarrays. We show how information obtained by these technologies has contributed to a better understanding of tumor and CTC biology
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Genome-Wide Gene Copy Number Analysis of Circulating Tumor Cells |
Mark Jesus M. Magbanua M.S. Ph.D.,John W. Park M.D. |
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Very little is known about the molecular biology of CTCs. The paucity of information can be largely attributed to the technical hurdles in isolating these extremely rare cells. Despite these challenges, there is a pressing need to elucidate the molecular characteristics of these tumor cells. In this chapter, we highlight recent studies on genome-wide gene copy number analysis of CTCs and comparisons with primary tumors. These initial studies serve as groundwork for future efforts in discovery and development of novel CTC-based genomic biomarkers. Further molecular profiling of CTCs may provide novel insights into mechanisms of disease progression and tumor evolution, and open new avenues for personalized treatment.
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Perspectives on the Functional Characterization and In Vitro Maintenance of Circulating Tumor Cells |
Anthony Williams Ph.D.,Ramdane Harouaka Ph.D.,Siyang Zheng Ph.D.,Chris Albanese Ph.D.,Richard Schleg |
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Circulating tumor cells (CTCs) that detach and migrate from primary tumors are implicated in the metastatic spread of cancer. The identification of CTCs in peripheral blood samples has been associated with poor survival outcomes in various cancer types. As a readily accessible source of tumor tissue there is a vast potential to develop CTCs as a biomarker to advance cancer diagnosis, prognosis and the development of novel and targeted therapies. The fact that CTCs occur as extremely rare events in whole blood presents a technical challenge for characterization, requiring enrichment techniques that are both highly sensitive and sufficiently specific. The culture and expansion of CTCs is desirable as a means of yielding a population suitable for comprehensive functional characterization and drug testing. Reports of successful in vitro culture of CTCs are rare, but various approaches have been attempted and significant progress has been made. The development of protocols for reliable and efficient culture of viable CTCs will advance our biological understanding of cancer metastasis and facilitate the development of personalized therapies.
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Prognostic Implications of CTC in Breast Cancer |
Jeffrey B. Smerage M.D., Ph.D. |
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Circulating tumor cells (CTCs) represent an important conceptual link between a primary tumor and the development of metastatic disease, and in the setting of metastatic disease CTC have the potential to reveal important insights into the biology and behavior of the cells undergoing the metastatic process and contributing to the resistance and progression of disease over time. In breast cancer the enumeration of CTC has been demonstrated to be a strong prognostic factor for both progression and survival. The finding of elevated CTC after one cycle of cytotoxic chemotherapy are associated with a particularly poor prognosis, suggesting the need for innovative drugs and treatment strategies. Although prognosis can be important in treatment planning, enumeration of CTC has not yet led to predictive models for the selection of specific drugs or for when to stop or switch the current therapy. CTC can be effective in defining when and how often to perform radiographic extent-of-disease scans. Given the relatively modest impact the CTC enumeration has had on clinical care, the focus has been the development of new platforms to increase sensitivity to allow there detection in a larger fract
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CTC in Advanced Breast Cancer Prognosis, Monitoring, and Clinical Utility |
Massimo Cristofanilli M.D., F.A.C.P. |
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Abstract
Circulating tumor cells (CTCs) are epithelial cells that can be found circulating in the blood of metastatic breast cancer patients and may represent a heterogeneous population including cancer stem cells and cells shed from the metastatic lesions. Interest and research continues in CTCs with the intent to detect and perform molecular analysis of those cells with the possibility to better understand the fundamental processes driving tumor metastasis. The technological advancement suggested the potential to measure the metastatic potential of a tumor at the single cell level rather than waiting until the cells established a metastatic lesion and proliferate until they are large enough to be visualized on imaging or cause symptoms. Therefore, earlier detection of these cells may be associated with more effective treatment of micrometastatic disease and lead to better outcomes. This chapter will provide an overview of the clinical utility of CTCs in breast cancer by reviewing the various techniques of CTC isolation; discussing their use as a prognostic indicator, as well as monitoring tool for response to therapy and detection of recurrence in the metastatic setting; reviewing their u
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Evolution of Metastatic Disease: The Need for Monitoring and Emerging Therapeutic Opportunities |
Bernhard Polzer M.D.,Christoph A. Klein M.D. |
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During the last few years tailored therapies have improved overall survival of patients with metastatic disease. However, iatrogenic selection pressure continues to drive the evolution of systemically spread cancer cells, resulting in the generation of aggressive and therapy-resistant tumor cells. The outcome is cancer relapse and death in the majority of patients. In early disease stages, (neo) adjuvant targeted therapies often fail for unknown reasons. Therefore, diagnostic and therapeutic strategies have to be reevaluated on the basis of an evolutionary concept of disease. This obviously implies the ability to monitor the molecular evolution of the disease. To this end, a novel diagnostic pathology for systemic cancer has to be developed that will enable precision medicine for cancer patients.
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CTCs for Biomarker and Companion Diagnostic Development |
Shih-Min A. Huang Ph.D.,Mark R. Lackner Ph.D. |
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Abstract
Circulating tumor cells (CTCs) were first recognized in the blood of cancer patients by Thomas Ashworth in 1869. Recent advances have propelled CTCs to center stage in diagnostic and translational research, largely owing to advances in isolation technology and increasing sensitivity of the various genomic, transcriptomic, and proteomic platforms. As we enter the era of personalized medicine, it is foreseeable that CTCs will become an integral component of clinical practice to not only understand disease evolution but also match patients with appropriate therapeutics..The current field is inundated with an enormous amount of data studying diverse aspects of CTC biology. In this chapter, we focus on recent developments in the incorporation of CTCs in oncology clinical studies that suggest promising utility for CTCs as pharmacodynamic and predictive biomarkers that can fundamentally aid decision making in clinical trials. In light of the complexity inherent in codeveloping in vitro diagnostic assays with therapeutic agents, we highlight key challenges and suggest solutions to enable the ultimate goal of developing CTCs as companion diagnostic assays for targeted oncology therapeutics.
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