This volume presents state-of-the-art information on each of the arms of the unfolded protein response (UPR), how their activation/repression are regulated, integrated, and coordinated, how UPR components affect cancer cell biology and responsiveness to therapeutic interventions, and how UPR components/activities offer potentially novel targets for drug discovery, repurposing, and development. The volume will provide the most recent information on the signaling and regulation of the UPR, explore examples of how the UPR and/or specific components contribute to cancer biology, and identify and explore specific examples of potently new actionable targets for drug discovery and development from within the UPR and its regulation. Unique to the volume will be a specific focus on the UPR and its role in cancer biology, as well as a discussion of the role of the UPR in drug responses and resistance in cancer.

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.

This volume is divided in six section covering the most experimental approaches involved in the study of the unfolded protein response (UPR) pathway. Chapters detail determination of unfolded protein levels, methods to study UPR signal transmission, analysing the outcomes of the UPR pathway activation, UPR studies in mammalian models, UPR in alternative models, and UPR and disease. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, The Unfolded Protein Response: Methods and Protocols aims to describe key methods and approaches used in the study of the UPR pathway and its complex cellular implications. Chapter 6 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. - Presents the most advanced information regarding the role of the autophagic system in life and death - Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment - Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ‘ER stress’. Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases.

This book provides research-oriented care providers with up-to-date information on the oral cancer patient population, the ways in which we are treating them, and the scientific approaches being pursued in order to improve survival and reduce treatment-related morbidity. The text is organized into three sections covering epidemiology and management, cancer development and biomarkers, and breaking developments and novel approaches for drug discovery. The first section includes discussion of the emerging role of HPV in oral cancer and explains the surgical, chemotherapy and radiation approaches to treatment. Aspects such as molecular progression, the role of cancer stem cells in tumor development, and the value of various biomarkers are then examined. The final section is devoted to the latest advances and covers, among other topics, current clinical trials, emerging drug targets, and targeting of the unfolded protein response and of mediators of coagulation.

Throughout history, arsenic has been used as an effective and lethal poison. Today, arsenic continues to present a real threat to human health all over the world, as it contaminates groundwater and food supplies. Handbook of Arsenic Toxicology presents the latest findings on arsenic, its chemistry, its sources and its acute and chronic effects on the environment and human health. The book takes readings systematically through the target organs, before detailing current preventative and counter measures. This reference enables readers to effectively assess the risks related to arsenic, and provide a comprehensive look at arsenic exposure, toxicity and toxicity prevention. - Brings together current findings on the effects of arsenic on the environment and human health - Includes state-of-the-art techniques in arsenic toxicokinetics, speciation and molecular mechanisms - Provides all the information needed for effective risk assessment, prevention and countermeasure