Targeting The Wnt 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 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

Dysregulation of Wnt signaling is known to be associated with various cancers. As such, identification of novel Wnt pathway targets in cancer and better characterization of already-known targets present exciting, emerging opportunities for cancer treatment. In this Special Issue, we feature papers which discuss the role of Wnt signaling and associated targets in cancer metabolism, tumor immune response, and tumor microenvironment. Papers discussing a range of Wnt-mediated cancers, including those of the colon, liver, pancreas, synovium, bladder, etc., are included.

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