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Selective Targeting to the Hyperactive ß-Catenin/T-Cell Factor Pathway in Colon Cancer Cells¹

Cancer Research Institute, University of California, San Francisco, San Francisco, California 94115

Many colon cancers suffer mutations in either the adenomatous polyposis coli or ß-catenin genes that lead to stabilization of ß-catenin and activation of downstream T-cell factor (Tcf) target genes. We have developed a novel approach targeting colon cancer cells based on their aberrant ß-catenin/Tcf signaling pathway. A recombinant adenovirus, in which an apoptosis gene fadd is under the control of the promoter containing Tcf-responsive elements, selectively and efficiently kills colon cancer cells in which the ß-catenin/Tcf pathway is hyperactivated. Our data therefore provide a conceptual proof that aberrantly activated Wnt/ß-catenin/Tcf pathways can be used to selectively target colon cancers.

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