Activation of the WNT signaling pathway has long been implicated in driving cancer pathogenesis from compelling evidence derived from complementary in vitro and animal studies. Moreover, there are extensive data supporting the nuclear localization of β-catenin, a surrogate marker frequently used as a read-out of WNT pathway activation, in addition to the overexpression of pathway activators and loss of pathway inhibitors in human cancers. Despite being most often linked with colorectal cancer, WNT pathway activation has now been associated with virtually every type of solid cancer that occurs in humans, although the frequency can vary dramatically among tumor subtypes and specific pathway components. These findings have significant implications regarding the mechanisms by which pathway activation might drive tumor development in specific tumor subtypes as well as the potential utility and impact of targeting this pathway therapeutically. In this chapter, we will summarize, both by tumor type and pathway components, the expansive evidence suggesting that the pathway is dysregulated in nearly half of all the most common types of human malignancies.
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