Targeting the Wnt Pathway in Cancer [Paperback]

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 b-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.

An Introduction to Wnt Signaling.-?Regulation of Wnt Secretion and Distribution.- Wnt Signaling in Stem Cells.- Crosstalk of the Wnt Signaling Pathway.- Dysregulation of the WNT Pathway in Solid Tumors.-?WNT/b-catenin Signaling in Leukemia.- Use of Genetically-engineered Mouse Models in Identification and Validation of Therapeutic Targets for Colon Cancer.- Targeting Wnt Signalling in Cancer.- Inhibiting the Wnt Signaling Pathway with Small Molecules.-?Targeting of Wnt Signaling Inside the Nucleus.-

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 lÓ'