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.

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.

Wnt proteins are signaling molecules that play critical roles during embryonic development and in the regeneration of adult tissues. They bind to Frizzled and LRP family receptors on the cell surface, triggering a series of events that cause ?-catenin to enter the nucleus and activate transcription factors that control cell fate and cell proliferation. Mutations in components of the Wnt pathway lead to developmental defects and are common in cancer. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology covers all aspects of canonical Wnt signaling, as well as ?-catenin-independent Wnt signaling and cross-talk with other pathways. The contributors examine the numerous Wnt ligands; their production, secretion, and interactions with components of the extracellular environment; and details of the downstream signaling pathways that mediate the effects of Wnt proteins on cells. The roles of Wnt signaling in stem cell self-renewal, cell polarity, body-axis specification, wound healing, and other aspects of normal development and physiology are also covered. This volume includes discussion of Wnt signaling in cancer, skeletal defects, neurological disorders, and other human disease states. Thus, it is an indispensable reference for cell and developmental biologists as well as those, especially in the fields of stem cell biology and regenerative medicine, who are interested in targeting the Wnt pathway for therapeutic purposes.

There have been tremendous recent advances in the pharmacotherapy, dose regimens, and combinations used to treat cancer and for the treatment or prevention of the spread of disease. As a direct result of these advances, there are an increasing number of cancer survivors, although research dealing with chemotherapy-induced pain is still in its early

The greatest mystery of life is how a single fertilized egg develops into a fully functioning, sometimes conscious multicellular organism. Embryogenesis Explained offers a new theory of how embryos build themselves, and combines simple physics with the most recent biochemical and genetic breakthroughs, based on the authors' prediction and then discovery of differentiation waves. They explain their ideas in a form accessible to the lay person and a broad spectrum of scientists and engineers. The diverse subjects of development, genetics and evolution, and their physics, are brought together to explain this major, previously unanswered scientific question of our time.As a follow up on The Hierarchical Genome, this book is a shorter but conceptually expanded work for the reader who is interested in science. It is useful as a starting point for the curious layman or the scientist or professional encountering the problem of embryogenesis without the formal biology background. There is also material useful for the seasoned biologist caught up in the new rush of information about the role of mechanics in developmental biology and cellular level mechanics in medicine.

This new volume of the renowned serial Current Topics in Developmental Biology covers the important features of growth factors in development. With an international board of authors, this volume will be invaluable for researchers in cell, developmental and molecular biology. - Provides researchers an overview and synthesis of the latest research findings and contemporary thought in the area - This volume provides an up-to-date and timely perspective