D-lactate and glycerol as potential biomarkers of sorafenib activity in hepatocellular carcinoma.

ABSTRACT: Sorafenib, a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), often encounters resistance within months of treatment, limiting its long-term efficacy. Despite extensive efforts, reliable plasma biomarkers to monitor drug activity remain elusive. Here, we demonstrate that metabolic reprogramming is a strategic response implemented by cancer cells to survive the therapeutic pressure. Sorafenib suppresses oxidative phosphorylation by disrupting electron transport chain supercomplex assembly and enhancing glycolysis. To mitigate the accumulation of harmful glycolytic byproducts such as advanced glycation end-products (AGEs), sorafenib-treated cells reroute excess dihydroxyacetone phosphate (DHAP) toward glycerol-3-phosphate (G3P) synthesis, supporting glycerolipid metabolism

SUBMITTER: Pedretti S 

PROVIDER: S-EPMC12202795 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature