Breaking through the transarterial chemoembolization resistance barrier: Reshaping the treatment path for advanced...

In this article we commented on an article published recently by Jiao et al. This retrospective study confirmed that the triple therapy of transarterial chemoembolization (TACE) combined with programmed death protein ligand 1 inhibitors and molecular targeted therapy can significantly reverse TACE resistance in advanced hepatocellular carcinoma. Compared with TACE alone, the triple therapy reduced the resistance rate from 38.8% to 9.7% and increased the median progression-free survival and median overall survival by 92.3% and 26.8%, respectively. TACE induces tumor antigen release and upregulates programmed death protein ligand 1, activating the effect of immune checkpoint inhibitors while molecular targeted therapy inhibits postembolization vascular regeneration, forming a dynamic synergistic network of embolization-immune activation-vascular inhibition. The maximum tumor diameter, capsule loss, and bilateral distribution were identified as independent predictors. This study provided level I evidence and promoted the transformation of advanced hepatocellular carcinoma treatment from single local intervention to an integrated model of local control-systemic treatment. In the future it will be necessary to analyze the dynamic evolution rules of the tumor microenvironment through cross-omics strategies, further explore biomarkers, optimize treatment sequences, and conduct multicenter prospective trials to verify long-term survival benefits and guide the optimization of individualized sequential treatment.