Stress Response Pathways In Cancer

It is now established that dysregulated cell stress response pathways play a critical role in tumorigenesis, and a refined mechanistic understanding of this phenomenon at the molecular level promises to open new avenues for targeted therapeutic strategies that may benefit cancer patients in the near future. Coauthored by recognized leaders in cancer research from five continents, this novel book provides a comprehensive perspective on cell stress response pathways and therapeutic opportunities. Focusing on the role of genotoxic, proteotoxic, oxidative, metabolic, and inflammatory stress in tumorigenesis, the book is essential reading for students, basic researchers, and biomedical health care professionals interested in cancer and therapeutic development.

In response to stress, cells can activate a myriad of signalling pathways to bring about a specific cellular outcome, including cell cycle arrest, DNA repair, senescence and apoptosis. This response is pivotal for tumour suppression as all of these outcomes result in restriction of the growth and/or elimination of damaged and pre-malignant cells. Thus, a large number of anti-cancer agents target specific components of stress response signalling pathways with the aim of causing tumour regression by stimulating cell death. However, the efficacy of these agents is often impaired due to mutations in genes that are involved in these stress-responsive signalling pathways and instead the oncogenic potential of a cell is increased leading to the initiation and/or progression of tumourigenesis. Moreover, these genetic defects can increase or contribute to resistance to chemotherapeutic agents and/or radiotherapy. Modulating the outcome of cellular stress responses towards cell death in tumour cells without affecting surrounding normal cells is thus one of the ultimate aims in the development of new cancer therapeutics. To achieve this aim, a detailed understanding of cellular stress response pathways and their aberrations in cancer is required. This Research topic aims to reflect the broadness and complexity of this important area of cancer research.

It is now established that the interplay between environmental exposure and molecular stress response pathways plays a critical role in skin health and disease, and a refined mechanistic understanding of this phenomenon at the molecular level promises to open new avenues for targeted therapeutic strategies that may benefit patients in the near future. Coauthored by recognized international leaders in molecular and clinical biomedical sciences, this novel book provides a comprehensive perspective on environmental exposure-induced skin stress response pathways. Focusing on molecular opportunities targeting skin stress response pathways that are involved in cutaneous barrier function and repair, antimicrobial defense, immune regulation, inflammation, and malignant progression, the book is essential reading for students, basic researchers, and biomedical health care professionals interested in skin health and disease with implications for small molecule therapeutic development.

Mammalian cells have evolved a complex multicomponent machinery that enables them to sense and respond to a wide variety of potentially toxic agents present in their environment. These stress responses are often associated with an increased cellular capacity to tolerate normally lethal levels of an insult. The realization that the mammalian stress response may be intimately linked with many human diseases, including rheumatoid arthritis, ischemia, fever, infection, and cancer, has led to an explosion of interest in this research area. Stress Response: Methods and Protocols brings together a diverse array of practical methodologies that may be employed to address various aspects of the response of mammalian cells to environmental stress. The p- tocols are carefully described by authors who have both devised and succe- fully employed them, and they represent a mixture not only of well-established techniques, but also new technologies at the leading edge of research. The areas covered include the detection and assay of stress-induced damage, the acti- tion of signal transduction pathways, stress-inducible gene expression, and stress protein function. Although no volume of this size can be comprehensive and the topics covered reflect a personal choice, it is hoped that it will prove of subst- tial interest and use to a wide range of research workers in the field.

Cellular Responses to Stress brings together a group of scientists who work on different but interrelated aspects of cellular stress responses. The book provides state-of-the-art information on the wide spectrum of ways in which cells can respond to different forms of stress induced by chemicals, oxidants, and DNA-damaging agents. Mechanisms are described that involve altered uptake and efflux of chemical agents, intracellular detoxification, and DNA damage responses. Many of these changes trigger a cascade of reactions mediated by stress-activated signaling pathways, which have the capacity to determine whether a cell will survive or die. The spectrum of topics covered in this book aims to provide a broad overview of our current knowledge of the different forms of adaptive response systems. It is hoped that this text will stimulate further research to establish the relative cellular role of specific response pathways and will enable us to gain a deeper understanding of the mechanisms that allow cells to live or die. This book will be valued by university researchers at all levels, industrial scientists in the pharmaceutical and biotechnology industries, and clinical researchers. Originally published in 1999. The Princeton Legacy Library uses the latest print-on-demand technology to again make available previously out-of-print books from the distinguished backlist of Princeton University Press. These editions preserve the original texts of these important books while presenting them in durable paperback and hardcover editions. The goal of the Princeton Legacy Library is to vastly increase access to the rich scholarly heritage found in the thousands of books published by Princeton University Press since its founding in 1905.

In recent years, increasing evidence has suggested that abnormal activation of signaling pathways is a critical event in cancer pathogenesis. In particular, activation of these pathways can lead to inappropriate cellular survival, proliferation, pluripotency, invasion, metastasis, and angiogenesis. Thus, understanding the mechanisms by which signaling pathways become subverted in a cancer cell can provide insight into critical events in cancer pathogenesis. Furthermore, as our ability to target specific molecular interactions advances, we now have the ability to design small molecules, protein therapeutics, and other forms of targeted therapies. By focusing on the specific molecular abnormalities in a cancer cell, these agents hold the potential to be much more effective and much less toxic than current cytotoxic therapies.

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.