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Among aberrantly regulated signaling pathways in cancer the WNT/β-catenin pathway plays an outstanding role,since it was shown to be critically involved in a very wide range of neoplasias.While the underlying mechanisms vary overexpression of WNT proteins was found to lead to active signaling in many of these diseases.Other cancers show a mutation in pathway members further downstream,such as APC,Axin or β-catenin,leading to signaling activation.Another known mechanism leading to aberrant activation of WNT/β-catenin signaling is the silencing of expression of negative WNT/β-catenin regulators,such as DKK or WIF1,by for example promoter hypermethylation.All these mechanisms result in a common consequence,the activation of TCF/LEF 1 transciption factors and subsequent target gene expression.Several of those target genes are known to be key players in tumorigenesis,such as c-myc,cyclin D1 or survivin.The variety of possible underlying mechanisms leading to β-catenin/TCF/LEF1 activation,offers different options to target the aberrantly activated pathway in order to prevent target gene expression and/or their gene products to carry out their tumorigenic function.