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.

In Vitro Toxicology Systems brings together important issues and considerations needed in order to develop a workable, reliable, integrated testing strategy for the replacement of animals in toxicity testing regimes. This thorough volume includes sections on in vitro models for systemic organ toxicity, neurotoxicity, sensory organs, immunotoxicity and reproductive toxicity and addresses how stem cells may be used going forward. The book also tackles difficult areas of toxicology such as carcinogenicity and nanotoxicology, with additional chapters dedicated to kinetics, metabolism, and in vitro in vivo extrapolation. The book also addresses biological processes such as stress response pathways and mechanistic biomarkers and how these can be uncovered and measured using high content approaches. Reliable and authoritative, In Vitro Toxicology Systems will be of benefit not only to students, scientists and regulators working in the field of chemical safety assessment but also to a wider scientific audience.

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.

One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."

Most cancer deaths are a result of metastasis. The spread of a primary tumor to colonize neighboring and distant organs is the relentless endgame that defines the neoplastic process. Patients who have been diagnosed with cancer are treated to prevent both the recurrence of the tumor at the site of origin and metastasis that would re-stage them as advanced stage IV cancer. Historically and still with some types of cancer, stage IV is perceived by patients as “terminal.” Fortunately, recent molecular therapies have extended the lives of patients with advanced cancer and reassuringly people living with metastatic disease increasingly visit our clinics. What is the path forward? Given that the consilience of science and medicine is a dynamic art from which therapies arise, it would be misguided to consider any single work adequate at capturing the horizon for research. So with humility we constructed this text as primer for scientists. It begins with a broad introduction to the clinical management of common cancers. This is intended to serve as a foundation for investigators to consider when developing basic science hypotheses. Unquestionably, medical and surgical care of cancer patients reveals biology and dictates how novel therapeutics will ultimately be evaluated in clinical trials. The second section of this text offers provocative and evolving insights that underscore the breadth of science involved in the elucidation of cancer metastasis biology. The text concludes with information that integrates scientific and clinical foundations to highlight translational research. This book serves as a framework for scientists to conceptualize clinical and translational knowledge on the complexity of disease that is metastatic cancer.