Notably, the widespread clinical adoption of targeted-immunotherapy combinations (e.g. VEGFR inhibitors with ICIs) in advanced HCC raises a critical unanswered question: Does ZFAS1 drive cross-therapeutic resistance via crosstalk with signaling networks such as the PI3K-AKT-mTOR or JAK-STAT pathways [95,96]? This evidence concerns the gene KDR and hepatocellular carcinoma.