Metastatic Progression And Tumour Heterogeneity

Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

Improved understanding of the cellular and molecular makeup of tumors in the last 30 years has unraveled a previously unexpected level of heterogeneity among tumor cells as well as within the tumor microenvironment. The concept of tumor heterogeneity underlines the realization that different tumors can display significant differences in their genomic content as well as in their overall behavior. Our capacity to better understand the heterogeneous make up of tumors has very important consequences on our ability to design efficient therapeutic strategies to improve patient survival. This book highlights several aspects of tumor heterogeneity in the context of metastatic development and summarize some of the challenges posed by heterogeneity for tumor diagnostics and therapeutic management of tumors.

This open access volume will introduce recent discoveries in cancer metabolism since the publication of the first edition in 2018, providing readers with an up-to-date understanding of developments in the field. Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, the authors delve into the complexity and diversity of cancer metabolism and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies for cancer treatment. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer treatment. This book has four major parts. Part one will cover the basic metabolism of cancer cells, followed by a discussion of the heterogeneity of cancer metabolism in part two. Part three addresses the relationship between cancer cells and cancer-associated fibroblasts, and the new part four will explore the metabolic interplay between cancer and other diseases. This new section makes the book unique from other texts currently available on the market. The second edition will be useful for cancer metabolism researchers, cancer biologists, epidemiologists, physicians, health care professionals in related disciplines, policymakers, marketing and economic strategists, among others. It may also be used in courses such as intro to cancer metabolism, cancer biology, and related biochemistry courses for undergraduate and graduate students.

Tumor cells have a remarkable ability to survive in harsh circumstances, resist treatment and evade regulatory mechanisms like apoptosis and therapy. They alter their metabolism in order to sustain metastatic progression and uncontrolled growth. Functional and phenotypic heterogeneity in tumor cells gives them metastatic potential, aggressiveness and the capability to resist treatment. This heterogeneity is governed by a range of intrinsic and extrinsic stimuli involving the ones from the tumor microenvironment. Various tumor cells can exhibit heterogeneous phenotypic and morphological profiles comprising gene expression, metastatic potential, metabolism, proliferation, cellular morphology and motility. It have been detected in many types of cancer including breast cancer, head and neck cancer, gynecological carcinoma, multiple myeloma, leukemia, prostate cancer, colon cancer, bladder, brain cancer and liposarcoma. This book contains some path-breaking studies on tumor heterogeneity. It strives to provide a fair idea about tumor heterogeneity and to help develop a better understanding of the diagnostics and therapeutic management of tumors. This book will help new researchers by foregrounding their knowledge in this area of study.

This book offers significant coverage on different aspects of cancer from risk factors to the mechanisms leading to tumor progression and metastasis. Although tremendous progress has been made in cancer research and treatment, cancer metastasis remains a major unmet clinical need. The life and death of many cancer patients hangs on the degree of metastasis. This book provides new perspectives for diagnosis and cancer therapy. It includes new technologies and a new basis for current cancer therapies. To guarantee the high quality of this book, important topics are included and rigorously discussed in a simple and authentic way. The book addresses important challenges governing tumor progression and metastasis and brings new responses to both diagnosis and therapy. This book is a great source of knowledge and will be useful for researchers, medical doctors, oncologists, graduate and medical students, continued medical educators, health care providers, and all individuals interested in understanding cancer and its challenges.

This book is aimed to summarise the key aspects of the role of circulating tumour cells (CTCs) in breast cancer, with special attention to their contribution to tumour progression and establishment of metastatic disease. We aim to give a clear overview of the knowledge about CTCs, framed in the context of breast cancer, by analysing basic and clinical research carried out so far. In a broader sense, we will address what are the main clinical needs of this disease based on its molecular heterogeneity (subtypes) and lay out the knowledge and understanding that CTCs are giving about it and how they are contributing and can still improve the better monitoring and management of breast cancer patients. We will discuss the evidences of the use of CTCs as a tool to monitor cancer progression and therapy response, based on the prognostic and predictive value they have, as well as a tool to unravel mechanisms of resistance to therapy and to identify new biomarkers allowing to predict therapy success. Moreover, we will analyse the main aspects of ongoing clinical trials and how they can contribute to determine the clinical utility of CTCs as a breast cancer biomarker. We will also touch upon general knowledge or basic notions of the biology of the metastatic process in epithelial cancers, in order to understand the origin and biology of CTCs. In this sense, we will pay special attention to EMT (epithelial to mesenchymal transition), dormancy and minimal residual disease, three key aspects that determine the outcome of the disease. We will also cover general aspects on the isolation and characterization techniques applies to the study of CTCs, and also the possibilities that the study of CTCs, as a biomarker with biological function, is opening in terms of understanding the biology of metastatic cells and the identification of therapeutic targets based on the functional and molecular characterization of CTCs. Lastly, we will try to foresee the future of CTCs in terms of clinical application and implementation in the clinical routine.

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 processes of tumor metastasis, apoptosis and anti-tumor immune response are among the most complex yet rapidly advancing fields in the area of cancer research. This monograph, with its leading authorship, presents a comprehensive coverage of the recent advances in the various key concepts in these fundamental aspects of human cancer. It contains state-of-the-science reviews on invasion, metastasis, angiogenesis, apoptosis and immunologic aspects related to cancer.