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.

This book presents a large amount of information related to the heat shock response and heat shock factor (HSF), describes core observations about molecular mechanisms and pathophysiological roles, and provides fundamental concepts on the basis of information from diverse aspects. This adaptive response to high temperature or protein misfolding is a fundamental mechanism to maintain the capacity of protein homeostasis, or proteostasis, and is evolutionally conserved among all living organisms, including bacteria and humans, on the earth. Furthermore, physiological and pathological roles of HSF have been extensively studied in fruit fly, worm, and mouse models. It has been revealed that HSF plays roles in development of the brain, reproductive and sensory organs, and in ageing, inflammation, and circadian rhythm. Analysis of the mechanisms have uncovered that HSF exerts a wide range of effects on gene expression and epigenetic status on the whole genome. Moreover, loss or gain of HSF function is also closely related to protein-misfolding diseases including neurodegenerative diseases, psychiatric diseases, heart diseases, and cancers. Therefore, HSF is now thought to be a promising therapeutic target for treatment of these refractory diseases. For undergraduate students, this is a highly understandable source of information on heart shock response and HSF, covering the basis of HSF biology, the physiological role of HSF, and disease associated with HSF function. This book not only serves as a guide to the heat shock response and HSF for students and young researchers in other fields, but also is a cornerstone for future work in the field related to the heat shock response and HSF.