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Targeted therapies such as oral tyrosine kinase inhibitors (TKIs) are the main therapeutic strategy effective for advanced hepatocellular carcinoma (HCC). Currently six tyrosine kinase inhibitors for HCC therapy have been approved. The newly approved first-line drug donafenib represent the major milestones in HCC therapeutics in recent years. However, drug resistance in HCC remains challenging due to random mutations in target receptors as well as downstream pathways. TKIs-based combinatorial therapies with immune checkpoint inhibitors such as PD-1/PD-L1 antibodies afford a promising strategy to further clinical application. Recent developments of nanoparticle-based TKI delivery techniques improve drug absorption and bioavailability, enhance efficient targeting delivery, prolonged circulation time, and reduce harmful side effects on normal tissues, which may improve the therapeutic efficacy of the TKIs. In this review, we summarize the milestones and recent progress in clinical trials of TKIs for HCC therapy. We also provide an overview of the novel nanoparticle-based TKI delivery techniques that enable efficient therapy.

Improving Outcomes of Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma: New Data and Ongoing Trials