Although PORCN inhibitors do not exhibit significant side effects in the guts of tumor‐burdened mice, they induce various on‐target dose‐limiting toxicities, including bone fractures.[20] Using a 3D‐organoid model, some researchers have demonstrated that 70% of CRC cases bearing APC mutations exhibit a favorable growth status independent of the Wnt pathway activators,[20, 21] which further limits the efficacy of Wnt pathway inhibitors. This evidence concerns the gene APC and colorectal carcinoma.