Integrating Combination Therapy and Smart Embolic Materials to Overcome the Therapeutic Ceiling of Transarterial Chemoembolization in Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) remains standard for intermediate-stage hepatocellular carcinoma (HCC), but its long-term efficacy is limited by post-embolic hypoxia-driven angiogenesis and high recurrence rates. Combining TACE with targeted therapy, immunotherapy, or ablation improves outcomes. Concurrently, smart embolic agents are transforming TACE from passive embolization into active modulation of the tumor microenvironment. This review systematically evaluates clinical evidence for TACE-based combinations and principles guiding individualized selection. We delineate synergistic mechanisms of TACE with systemic and locoregional therapies, and highlight functional design of novel embolic materials. Although some triplet regimens have shown progression-free survival benefits, overall survival superiority remains unproven, as exemplified by the negative OS outcome in the LEAP-012 trial. However, the available network meta-analyses are constrained by substantial heterogeneity in study design, TACE protocols, and outcome definitions, warranting cautious interpretation. Finally, we propose a multidisciplinary paradigm integrating interventional radiology, diagnostic imaging, and biomaterials science. The convergence of material innovation and combination optimization holds promise for overcoming TACE's therapeutic ceiling.