Targeting The Wnt Catenin Signaling Pathway In Cancer

Inappropriate activation of the Wnt signaling pathway is observed in many human cancers and is sufficient to drive tumor initiation and progression in numerous contexts. Multiple mechanisms, such as overexpression of Wnt ligands, inactivation of the APC and Axin tumor suppressors, and mutation of -catenin, are responsible for pathway activation in tumor cells. The development of potent Wnt pathway antagonists for therapeutic use has been a major effort for investigators in both academia and industry in recent years. This book will provide an overview of the Wnt pathway as a therapeutic target for cancer, and discuss the preclinical development of inhibitors specifically directed to upstream and downstream components of the pathway.

Inappropriate activation of the Wnt signaling pathway is observed in many human cancers and is sufficient to drive tumor initiation and progression in numerous contexts. Multiple mechanisms, such as overexpression of Wnt ligands, inactivation of the APC and Axin tumor suppressors, and mutation of -catenin, are responsible for pathway activation in tumor cells. The development of potent Wnt pathway antagonists for therapeutic use has been a major effort for investigators in both academia and industry in recent years. This book will provide an overview of the Wnt pathway as a therapeutic target for cancer, and discuss the preclinical development of inhibitors specifically directed to upstream and downstream components of the pathway.

This book discusses the recent developments in the therapeutic implications of cancer stem cells for the effective diagnosis, prognosis, and treatment of cancer. It summarizes the various stem cells of common cancers including colon, pancreas, lungs, prostate, melanoma, and glioblastoma, and reviews the potential role of cancer stem cells in tissue aggressiveness, examining the functional contribution of cancer stem cells in the establishment and recurrence of cancerous tumors. Further, it explores the potential of cancer stem cells as novel therapeutic targets for the treatment and prevention of tumor progression. The book also discusses the various approaches for detecting, isolating, and characterizing different cancer stem cells and signaling pathways that control their replication, survival, and differentiation. Lastly, it explores the key features and mechanisms of drug resistance, chemo-resistance, and radio-resistance in cancer stem cells to improve therapeutic rationale.

WNT Signaling, Volume 153, the latest release in the Progress in Molecular Biology and Translational Science series, seeks to provide the most topical, informative, and exciting monographs available on a wide variety of research topics related to prions, viruses, bacteria and eukaryotes. The series provides readers with in-depth knowledge of important molecular biological aspects of organismal physiology and function, along with insights into how this knowledge may be applied to understand and ameliorate human disease. Each volume is edited by an internationally recognized expert who selects contributors at the forefront of a field. Accessible content that ideal for students and researchers alike Written by leading authorities in the field

This book reflects the state of the art of our understanding of the WNT signaling system, which comprises a network of signaling pathways initiated by the secreted WNT lipoglycoproteins, which are crucial for embryonal development, stem cell regulation, tissue homeostasis and repair. Dysfunction of this evolutionarily conserved signaling system leads to many diseases including developmental disorders, diverse forms of cancer, fibrosis, neurodegenerative disease and many more. The WNT signaling system is built upon 19 mammalian, secreted WNT lipoglycoproteins that interact with a plethora of distinct receptors, such as the G protein-coupled receptors called Frizzleds (FZD1-10), LDL receptor-like proteins (LRP5/6), receptor tyrosine kinases (ROR1, 2, RYK and PTK7). In addition, WNT pathways are tightly regulated by many secreted and cell-intrinsic negative regulators, such as soluble FZD-related proteins (SFRPs), Dickkopfs (DKKs), WNT-inhibitory proteins, TIKI, RNF43 and more. Understanding the basic mechanism in terms of receptor-ligand interaction, receptor selectivity, signal initiation and desensitization remain poorly understood, even though substantial advances have been made the recent years. Due to the involvement of the WNT signaling system in human disease, it appears obvious to target diverse branches pharmacologically and therapeutically. However, given the complexity of the system and its importance for stem cell regulation and tissue maintenance, therapy comes with obvious risks for severe side effects. The field is addressing the challenge to identify suitable targets and selective compounds for therapy allowing disease-selective therapeutic effects and balancing unwanted side effects. This book summarizes the current understanding of the basic and applied pharmacology in the WNT signaling system and bridges disciplines such as pharmacology, physiology, neurosciences, oncology and drug development.

Advances in Stem Cells and Their Niches addresses stem cells during development, homeostasis, and disease/injury of the respective organs, presenting new developments in the field, including new data on disease and clinical applications. Video content illustrates such areas as protocols, transplantation techniques, and work with mice. Explores not only reviews of research, but also shares methods, protocols, and transplantation techniques Contains video content to illustrate such areas as protocols, transplantation techniques, and work with mice Each volume concentrates on one organ, making this a unique publication

Wnt signaling in Development and Disease: Molecular Mechanisms and Biological Functions reviews the core topics in Wnt signaling, from molecular pathway mechanisms to its role in embryogenesis, adult tissue homeostasis, and chronic disease. Written by a team of expert reviewers, the book provides clear and concise coverage of the core foundations of Wnt signaling before advancing to discussion of cutting-edge scientific research. Focused on the biological insights and current scientific questions of Wnt signaling, this book will be a comprehensive and definitive resource for a wide range of researchers and students in cell signaling, cell physiology, developmental biology, and biomedical engineering, as well as anyone interested in learning more about this important and complex protein network. • A definitive source of information on Wnt signaling and its role in development and disease, written by leaders in the field. • Explores the role of Wnt signaling in chronic disease such as melanoma, colorectal cancer, dementia, and psychiatric diseases • Reviews the complex processes of signal integration and regulation • Features broad discussion of Wnt signaling biology as well as detailed discussion of the pathway’s role in diseases and potential clinical applications.