In human breast cancer cells, the ADAM10 and ADAM17 inhibitor, INCB3619, along with a lapatinib‐like dual inhibitor of endothelial growth factor receptor and HER‐2/neu kinases, demonstrated synergistic growth inhibition.[48] Aderbasib, another inhibitor of ADAM10 and ADAM17, overcomes endothelial growth factor receptor inhibitor resistance and enhance fluorouracil sensitivity in CRC.[63] Simultaneously, using a CRC organoid model in vitro and in vivo, we observed that adavivint enhanced FOLFOX sensitivity by suppressing ADAM10/NOTCH2 signaling‐mediated regulation of Wnt target genes. Here, NOTCH2 is linked to colorectal carcinoma.