Biblioteca Virtual en Salud

The Wnt pathway is an evolutionarily conservedsignaling network that is critical for mammalian development andadult tissue maintenance, and, importantly, hyperactivated in mosthuman cancers. Almost two decades of study has confirmed that Wntsignaling is necessary and sufficient for cancer pathogenesis inmultiple in vitro and in vivo models systems, suggesting that thepathway represents an attractive therapeutic target.ÿ Recentefforts have focused on innovative strategies to antagonize Wntsignaling at various levels of the pathway - from attenuating theextracellular signaling through the Wnt receptors to modulating thecatenin destruction complex to blocking catenin-mediatedtranscription. Many of these approaches have been largelysuccessful in preclinical validation studies and have been met withconsiderable enthusiasm to move forward into clinical trials. Inthis book, we highlight the recent advances in our understanding ofthe complexity of the Wnt pathway, particularly its intricateregulation and cross-talk with other key signal transductionpathways in normal and tumor cells. As a way to comprehend the roleof Wnt pathway activation in tumor initiation and progression, wediscuss the importance of Wnt signaling in embryonic and tissuedevelopment and stem cell maintenance and self-renewal. Theevidence for aberrant Wnt pathway activation in human solid andhematopoietic cancers, as well as a few of the genetic mouse modelsthat mimic the Wnt pathway deregulation observed in some of thesetumor types, is reviewed. Lastly, we summarize the current statusof the development of Wnt pathway inhibitors, their efficacy inpreclinical models and their potential as therapeutic agents forcancer. It is an exciting time in the Wnt signaling field - onethat represents a key crossroad between dissecting the moleculardetails of the pathway and translating that work into promisingtargeted tumor therapies - that is likely to profoundly impact thisresearch area for years to come.