The clinical relevance of the development of Wnt signaling inhibitors which work in a constitutively activated setting is tremendous, since mutations in the Wnt-signaling pathway are not only the first genetic alterations in the adenoma-carcinoma sequence, but advanced colorectal cancers with mutations in APC or CTNNB1 remain dependent on upstream Wnt signaling activity. The gene discussed is CTNNB1; the disease is carcinoma.