Targeting the Wnt Pathway in Cancer

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ISBN: 1441980229
ISBN 13: 9781441980229
Herausgeber: Kathleen H Goss/Michael Kahn
Verlag: Springer Verlag GmbH
Umfang: xi, 240 S., 4 s/w Tab.
Erscheinungsdatum: 28.01.2011
Auflage: 1/2011
Produktform: Gebunden/Hardback
Einband: GEB

The Wnt pathway is an evolutionarily conserved signaling network that is critical for mammalian development and adult tissue maintenance, and, importantly, hyperactivated in most human cancers. Almost two decades of study has confirmed that Wnt signaling is necessary and sufficient for cancer pathogenesis in multiple in vitro and in vivo models systems, suggesting that the pathway represents an attractive therapeutic target.  Recent efforts have focused on innovative strategies to antagonize Wnt signaling at various levels of the pathway – from attenuating the extracellular signaling through the Wnt receptors to modulating the catenin destruction complex to blocking catenin-mediated transcription. Many of these approaches have been largely successful in preclinical validation studies and have been met with considerable enthusiasm to move forward into clinical trials. In this book, we highlight the recent advances in our understanding of the complexity of the Wnt pathway, particularly its intricate regulation and cross-talk with other key signal transduction pathways in normal and tumor cells. As a way to comprehend the role of Wnt pathway activation in tumor initiation and progression, we discuss the importance of Wnt signaling in embryonic and tissue development and stem cell maintenance and self-renewal. The evidence for aberrant Wnt pathway activation in human solid and hematopoietic cancers, as well as a few of the genetic mouse models that mimic the Wnt pathway deregulation observed in some of these tumor types, is reviewed. Lastly, we summarize the current status of the development of Wnt pathway inhibitors, their efficacy in preclinical models and their potential as therapeutic agents for cancer. It is an exciting time in the Wnt signaling field – one that represents a key crossroad between dissecting the molecular details of the pathway and translating that work into promising targeted tumor therapies – that is likely to profoundly impact this research area for years to come.

Artikelnummer: 1600389 Kategorie:

Beschreibung

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.

Inhaltsverzeichnis

Chapter 1.  An Introduction to Wnt Signaling Paul Polakis   Chapter 2.  Regulation of Wnt Secretion and Distribution Xiaofang Tang Xiaolan Fan and Xinhua Lin   Chapter 3. Wnt Signaling in Stem Cells Philipp C. Manegold, Jia-Ling and Teo Michael KahnChapter 7.  Use of Genetically-engineered Mouse Models in Identification and Validation of Therapeutic Targets for Colon Cancer Masahiro Aoki and Makoto Mark Taketo   Chapter 8.  Targeting Wnt Signalling in Cancer Aliaksei Holik and Alan R. Clarke Cardiff School of Biosciences, Cardiff University,Cardiff, UK   Chapter 9.  Inhibiting the Wnt Signaling Pathway with Small Molecules  Ho-Jin Lee, Xinxin Zhang, and Jie J. Zheng   Chapter 10.  Targeting of Wnt Signaling Inside the Nucleus Miki Shitashige and Tesshi Yamada Markus Müschen Chapter 7.  Use of Genetically-engineered Mouse Models in Identification and Validation of Therapeutic Targets for Colon Cancer Masahiro Aoki and Makoto Mark Taketo   Chapter 8.  Targeting Wnt Signalling in Cancer Aliaksei Holik and Alan R. Clarke Cardiff School of Biosciences, Cardiff University,Cardiff, UK   Chapter 9.  Inhibiting the Wnt Signaling Pathway with Small Molecules  Ho-Jin Lee, Xinxin Zhang, and Jie J. Zheng   Chapter 10.  Targeting of Wnt Signaling Inside the Nucleus Miki Shitashige and Tesshi Yamada   Chapter 4. Crosstalk of the Wnt Signaling Pathway Michael Thompson, Kari Nejak-Bowen, Satdarshan P. S. Monga   Chapter 5.  Dysregulation of the WNT Pathway in Solid Tumors Jenifer R. Prosperi, Hue H. Luu and Kathleen H. Goss   Chapter 6.  WNT/b-catenin Signaling in Leukemia Markus Müschen Chapter 7.  Use of Genetically-engineered Mouse Models in Identification and Validation of Therapeutic Targets for Colon Cancer Masahiro Aoki and Makoto Mark Taketo   Chapter 8.  Targeting Wnt Signalling in Cancer Aliaksei Holik and Alan R. Clarke Cardiff School of Biosciences, Cardiff University,Cardiff, UK   Chapter 9.  Inhibiting the Wnt Signaling Pathway with Small Molecules  Ho-Jin Lee, Xinxin Zhang, and Jie J. Zheng   Chapter 10.  Targeting of Wnt Signaling Inside the Nucleus Miki Shitashige and Tesshi Yamada

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