Longevity & AgingBlocking ACLY Enzyme Slashes Liver Cancer Tumors and Reboots Immune Attack
Researchers at McMaster University identified a novel small-molecule inhibitor, EVT0185, that blocks ATP citrate lyase (ACLY), a metabolic enzyme overexpressed in liver cancer. In three mouse models of MASH-driven hepatocellular carcinoma (HCC), oral EVT0185 dramatically reduced tumor burden, enhanced the effects of tyrosine kinase inhibitors and immunotherapy, and triggered immune infiltration via increased CXCL13 chemokine and B cell recruitment to tumors. Genetic deletion of ACLY in hepatocytes achieved similar results. Cryo-EM structural analysis revealed EVT0185 is converted to a CoA thioester in the liver and binds directly to ACLY's CoA-binding site. These findings show that targeting tumor metabolism can rewire the immune microenvironment and suppress liver cancer progression.
