HKDC1-Mediated Polyamine Rewiring Drives Lenvatinib Resistance and Immune Escape in Hepatocellular Carcinoma - PubMed
14 hours ago
- #Polyamine Metabolism
- #Lenvatinib Resistance
- #Hepatocellular Carcinoma
- HKDC1 is upregulated in lenvatinib-resistant (LR) hepatocellular carcinoma (HCC) and is transcriptionally activated by USF1.
- HKDC1 promotes SMS-mediated polyamine rewiring, impairing CD8+ T-cell metabolism, which can be reversed by HKDC1 knockdown or spermidine (SPD).
- SPD synergizes with lenvatinib, inducing autophagy and suppressing tumor growth in vitro and in vivo.
- High HKDC1 levels predict poor response and survival in HCC patients treated with lenvatinib plus PD-1 blockade.
- The USF1/HKDC1/SMS axis links polyamine metabolism to immune dysfunction and lenvatinib resistance, suggesting HKDC1 as a predictive biomarker and therapeutic target.