Novel therapeutic features of disulfiram against hepatocellular carcinoma cells with inhibitory effects on a disintegrin and metalloproteinase 10.

Our previous genome-wide association study identified the anti-tumor ligand MHC class I polypeptide-related sequence A () as a susceptibility gene for hepatitis C virus-induced hepatocellular carcinoma (HCC). We subsequently proved that pharmacological restoration of membrane-bound MICA in HCC cells boosted natural killer cell-mediated anti-cancer effects, confirming that a MICA sheddase, a disintegrin and metalloproteinase 10 (ADAM10), is a therapeutic target. We here searched for approved drugs with inhibitory effects on ADAM10 , and the anti-alcoholism agent, disulfiram, was identified.

Predominance of regorafenib over sorafenib: Restoration of membrane-bound MICA in hepatocellular carcinoma cells.

Background And Aim: The multi-kinase inhibitor regorafenib (REG) was recently demonstrated to be effective in patients with sorafenib (SOR)-resistant hepatocellular carcinoma (HCC). Interestingly, SOR is known to enhance the accumulation of membrane-bound MHC class I polypeptide-related sequence A (mMICA) in HCC cells and to block the production of soluble MICA (sMICA), an immunological decoy. In addition, MICA is associated with HCC in patients with chronic hepatitis C.