Treatment options after primary or secondary drug resistance to targeted immunotherapy in hepatocellular carcinoma
LIU Xiu-feng
ZHU Yan
HAN Ning
YAO Lin
WANG Bi-bo
Abstract：In recent years,significant progress has been made in targeted combined immunotherapy for advanced hepatocellular carcinoma(HCC).However,the treatment response rate remains around 30％,with a median progression-free survival of 6 to 9 months.Additionally,approximately 20％of patients develop resistance to initial immunotherapy,making the selection of subsequent treatment options a critical clinical challenge.The failure of targeted combined immunotherapy primarily manifests as primary resistance and secondary resistance.Primary resistance is often associated with reduced tumor immunogenicity,including low expression of neoantigens,alterations in antigen presentation,and the expression of immune co-inhibitory signals.Secondary resistance may be related to the clonal evolution of the tumor towards a low immunogenicity phenotype following immunotherapy.Currently,there are no standardized clinical strategies to address these resistance mechanisms.The progression patterns of HCC can be categorized into intrahepatic progression,extrahepatic progression,new intrahepatic lesions,and new extrahepatic lesions,with significant differences in prognosis based on these patterns.Patients with intrahepatic progression or new extrahepatic lesions tend to have a relatively favorable post-progression survival,while the presence of new vascular invasion indicates a poor prognosis.Future clinical research and practice must focus on more precise and individualized treatment approaches,considering immune microenvironment reprogramming,etiological differences,and a multidisciplinary treatment framework.Specifically,for HCC patients with drug resistance,combining local treatments such as transarterial chemoembolization(TACE)or hepatic arterial infusion chemotherapy(HAIC)may improve survival outcomes.The role of targeted combined immunotherapy in the overall management of HCC is gradually being recognized,but further exploration is needed to establish standardized post-treatment strategies.
Keywords：hepatocellular carcinomaimmunotherapytarget therapyprimary resistancesecondary resistance
Publication Date：2024-09-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 1031-1037 )