The role of ADAM8 in intrahepatic cholangiocarcinoma

Currently, there are no approved first-line targeted inhibitors for ICC. ADAM8 is one of the most frequently over-expressed proteins in human intrahepatic cholangiocarcinoma (ICC). This review examines the potential of ADAM8 as a direct therapeutic target for ICC, emphasizing its downstream impact on Notch and Integrin signaling pathways. Collectively, these findings suggest ADAM8 may represent a novel strategy for ICC management. We have consolidated pre-clinical research on ADAM8 inhibitors, which demonstrate inhibitory effects on epithelial mesenchymal transition (EMT) and tumor angiogenesis by cleaving substrates such as CHL1 and CD23 to form their active fragments. And its substrate form may be monomers, dimers, or even polymers. This review provides a critical discussion of the therapeutic potential of ADAM8 inhibitors in ICC. However, further challenges remain, including enhancing inhibitor specificity, conducting long-term studies to thoroughly evaluate the benefits and risks associated with targeting ADAM8.