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Protein homeostasis, or “Proteostasis”, lies at the heart of human health and disease. From the folding of single polypeptide chains into functional proteins, to the regulation of intracellular signaling pathways, to the secreted signals that coordinate cells in tissues and throughout the body, the proteostasis network operates to support cell health and physiological fitness. However, cancer cells also hijack the proteostasis network and many of these same processes to sustain the growth and spread of tumors. The chapters in this book are written by world experts in the many facets of the proteostasis network. They describe cutting-edge insights into the structure and function of the major chaperone and degradation systems in healthy cells and how these systems are co-opted in cancer cells and the cells of the tumor microenvironment. The chapters also cover therapeutic interventions such as the FDA-approved proteasome inhibitors Velcade and Krypolis as well as other therapies currently under clinical investigation to disarm the ability of the proteostasis network to support malignancy. This compendium is the first of its kind and aims to serve as a reference manual for active investigators and a primer for newcomers to the field. This book is dedicated to the memory of Susan Lindquist, a pioneer of the proteostasis field and a champion of the power of basic scientific inquiry to unlock the mechanisms of human disease. The chapter “Reflections and Outlook on Targeting HSP90, HSP70 and HSF1 in Cancer: A Personal Perspective” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Heat shock proteins are emerging as important molecules in the development of cancer and as key targets in cancer therapy. These proteins enhance the growth of cancer cells and protect tumors from treatments such as drugs or surgery. However, new drugs have recently been developed particularly those targeting heat shock protein 90. As heat shock protein 90 functions to stabilize many of the oncogenes and growth promoting proteins in cancer cells, such drugs have broad specificity in many types of cancer cell and offer the possibility of evading the development of resistance through point mutation or use of compensatory pathways. Heat shock proteins have a further property that makes them tempting targets in cancer immunotherapy. These proteins have the ability to induce an inflammatory response when released in tumors and to carry tumor antigens to antigen presenting cells. They have thus become important components of anticancer vaccines. Overall, heat shock proteins are important new targets in molecular cancer therapy and can be approached in a number of contrasting approaches to therapy.
This book makes a novel synthesis of the molecular aspects of the stress response and long term adaptation processes with the system biology approach of biological networks. Authored by an exciting mixture of top experts and young rising stars, it provides a comprehensive summary of the field and identifies future trends.
Hsp90 in Cancer: Beyond the Usual Suspects, the latest volume in the Advances in Cancer Research series, focuses on the multifunctional molecular chaperone Hsp90 which regulates the post-translational stability and function of a broad repertoire of client proteins and discusses some of the lesser-known aspects of how Hsp90 and its related family members enable oncogenic transformation and malignant progression. - Focuses on the multifunctional molecular chaperone Hsp90 which regulates the post-translational stability and function of a broad repertoire of client proteins - Highlights the rapidly evolving understanding of the fundamental roles of Hsp90 in cancer biology - Discusses the lesser-known aspects of how Hsp90 and its related family members enable oncogenic transformation and malignant progression
Nearly a century of scientific research has revealed that mitochondrial dysfunction is one of the most common and consistent phenotypes of cancer cells. A number of notable differences in the mitochondria of normal and cancer cells have been described. These include differences in mitochondrial metabolic activity, molecular composition of mitochondria and mtDNA sequence, as well as in alteration of nuclear genes encoding mitochondrial proteins. This book, Mitochondria and Cancer, edited by Keshav K. Singh and Leslie C. Costello, presents thorough analyses of mitochondrial dysfunction as one of the hallmarks of cancer, discusses the clinical implications of mitochondrial defects in cancer, and as unique cellular targets for novel and selective anti-cancer therapy.
This edited volume offers an insightful overview of contemporary research on signaling pathways. These signaling processes are the comprehensive mechanisms by which all cellular organisms communicate internally and externally with their microenvironment. The volume is focused on heat shock proteins (HSP), which are uniquely involved in a number of critical signaling pathways. Errors in signaling pathways and in the processing of cellular information are known to be responsible for the majority of diseases including cancer, inflammatory and neurological disorders. The knowledge gained from better understanding these mechanisms can help in elucidating disease processes and will assist in development and design of novel targeted treatment therapies to combat human diseases and disorders. Key basic and clinical research laboratories from major universities, academic medical hospitals, biotechnology and pharmaceutical laboratories around the world have contributed chapters that review present research activity and importantly project the field into the future. The book is a must read for graduate students. medical students, basic science researchers and postdoctoral scholars in the fields of Translational Medicine, Clinical Research, Human Physiology, Biotechnology, Cell & Molecular Medicine, Pharmaceutical Scientists and Researchers involved in Drug Discovery.
Immune Surveillance deals with the issues regarding tumor immunology and surveillance, in which the central theme is all about the life span of the mammalian host that is depleted by the environment with mutagenic agents and solutions. The book is divided into six chapters. It includes discussions on the organization and modulation of cell membrane receptors, as well as the origin and expression of membrane antigens. It also covers the topics on the triggering mechanisms for and effector mechanisms activated by the cellular recognition. These topics analyze and evaluate alternatives for the recognition and destruction mechanisms in the knowledge of cell cooperation and requirements for immune recognition. A chapter provides discourse on a solution for the paradox of thriving tumors based on the demonstrable in vitro host immunity. Another discusses the generation of antibody diversity and the theory of self-tolerance. The last chapter explains the evaluation of the evidence for immune surveillance. This reference will be invaluable to those who specialize in immunology.
Given the very limited capacity of regeneration in the brain, protecting neurons that are on the brink of death is a major challenge for basic and clinical neuroscience, with implications for a broad spectrum of acute and chronic neurological and psychiatric diseases. This book brings together leading experts from neurobiology, neurophysiology, neuropharmacology, neuroimmunology and clinical neuroscience to highlight the most recent milestones in this rapidly evolving field. The book will serve as a reference for both basic neuroscientists and clinicians interested in an authoritative update on the molecular and cellular biology of neuroprotection and its promises for new therapeutic strategies.
Intracellular Receptors: New Instruments for a Symphony of Signals In the late eighteenth century, it was proposed on theoretical grounds that each of the body's organs, beginning with the brain, must be "a factory and laboratory of a specific humor which it returns to the blood", and that these circulating signals "are indispensable for the life of the whole" (Bordeu 1775). During the nineteenth cen tury, some remarkable physiological experiments revealed the actions of humoral factors that affected the for and function of multiple tissues, organs and organ sys tems within the body (Berthold 1849); much later, the chemical and molecular na ture of some of those factors was determined. Against this deep historical backdrop of the founding studies of intercellular signaling, molecular biology sprang into existence a mere forty years ago, rooted in the revelation of regulable gene expression in bacteria. But contemporaneous with those classical analyses of transcriptional regulation of the lactose operon, the mod em era of signal transduction was inaugurated by the identification of cAMP as a second messenger -- an intracellular mediator of hormonal activation of glycogen catabolism (Sutherland and RaIl 1960). Later in that same decade, it emerged that cAMP is a critical signal not only in metazoans, but even in bacteria, where it serves an analogous function as a critical switch that activates expression of genes re quired for catabolism of complex carbon sources, including those of the lactose operon.
The book is dedicated to the topical area of biology and medicine and the role of stress proteins HSP70 in the regulation of intracellular protein homeostasis, signaling transduction and cell protection. The book is divided into chapters, which describe the discovery of HSP70 and its molecular structure, the mechanism of the synthesis and function in normal and damaged cells, examine the role of HSP70 in immunity, cancerogenesis, aging, Alzheimer's disease and cardiac surgery. In this book, the author looks at HSP70 as a factor which prevents the transformation of homeostasis mechanisms of intracellular proteins into a link in the pathogenesis of a disease.