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

This book will deal with heat shock proteins and more generally with stress-related inducible gene expression as a pleiotropic adaptive response to stress. It presents a textbook-like overview of the field not only to heat shock experts, but to physiologists, pharmacologists, physicians, neuropsychologists and others as well. It is intended to be a state-of-the-art and perspective book rather than an up-to-date presentation of recent data. It should provide a basis for new experimental approaches to fields at the edge of the classical heat shock field. Drugs, UV irradiation and environmental toxics will considered as important modulators of the stress response. Radical scavengers such as superoxide dismutases and inducible regulatory proteins of metallic ion status such as ferritin as well as immunophilins and protein disulfide isomerases will be considered within the frame of stress proteins. The potential practical applications of heat shock proteins in toxicology and medicine for the diagnosis, prognosis and eventually therapy of clinical conditions associated with an increased oxidative burden will be outlined. The role of heat shock proteins in the modulation of immune responses will also be included. The book considers heat shock from a broad perspective including fields for which heat-shock may become of importance in the very near future such as cellular responses to environmental stresses and complex stress responses under specific conditions. It was also felt timely to incorporate a whole section on medical and technological applications of stress proteins.

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.

The book Heat Shock Proteins and Stress provides the most comprehensive review on contemporary knowledge on the role of HSP in Stress. Using an integrative approach to understanding the regulation of HSP responses, the contributors provide a synopsis of novel mechanisms by which HSP responses are regulated under normal physiological and pathophysiological conditions. Key basic and clinical research laboratories from major universities and academic medical hospitals around the world contribute chapters that review present research activity and importantly project the field into the future. The book is a must read for researchers, postdoctoral fellows and graduate students in the fields of Translational Medicine, Clinical Psychologists, Human Physiology, Zoologists, Botanists, Biotechnology, Molecular Medicine, Infectious Diseases Experts and Pathologists.