ITCH and hepatocellular carcinoma: Given the established role of UPS in mediating chemotherapy resistance, we hypothesize that in the unique tumor microenvironment of post-TACE HCC, SERPINA1 may confer resistance by a novel mechanism: competitively inhibiting ITCH-mediated ubiquitination of ITGB3 to stabilize it, thereby activating downstream survival pathways-a mechanistic insight that could unveil novel therapeutic vulnerabilities in HCC.