Exploring combination therapy centered on targeted immunotherapy for advanced hepatocellular carcinoma: a beacon of hope

Abstract Hepatocellular carcinoma (HCC) is an aggressive malignancy that is highly prevalent worldwide. It is often diagnosed at an advanced stage, which poses challenges for curative treatment and leads to an unfavorable prognosis. The introduction of targeted therapy drugs, such as tyrosine kinase inhibitors, and immunotherapeutic drugs, including immune checkpoint inhibitors, has substantially improved the therapeutic effectiveness for advanced HCC. However, their efficacy remains suboptimal, owing to challenges related to patient responsiveness and drug resistance. To address these challenges, researchers have investigated combination therapies, including targeted immunotherapy, and triple therapies based on targeted immunotherapy, such as a combination of radiotherapy and targeted immunotherapy. In addition, they conducted a comprehensive investigation of potential new targets and drugs, yielding a series of significant findings. This review presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies, immunotherapies, and combination therapies. It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.