Using a genome‐wide clustered regularly interspaced palindromic repeat (CRISPR) approach, a previous study demonstrated that the WNT receptor FZD5 signaling circuit is vulnerable in RNF43‐mutated pancreatic cancer.[10] To identify the altered signaling pathways and druggable targets in RNF43‐mutated cancer cells, we performed kinase inhibitor library screening in RNF43‐mutated pancreatic cancer cells (AsPC‐1 and HPAF‐II) and RNF43‐wild‐type PANC‐1 cells. Here, RNF43 is linked to familial pancreatic carcinoma.