Preventing the secretion of Wnts by inhibiting the PORCN enzymatic activity inhibits both canonical and non-canonical Wnt signaling; hence PORCN inhibitors have shown high efficacy in the subset of cancers driven by high Wnt signaling including molecularly defined colorectal cancers with R-spondin translocations and pancreatic cancers with RNF43 mutations [11]. Here, PORCN is linked to colorectal cancer.