Abstract
Hepatocellular carcinoma (HCC) is one of the common and fatal malignancies, which is a significant global health problem. The clinical applicability of traditional surgery and other locoregional therapies is limited, and these therapeutic strategies are far from satisfactory in improving the outcomes of advanced HCC. In the past decade, targeted therapy had made a ground-breaking progress in advanced HCC. Those targeted therapies exert antitumor effects through specific signals, including anti-angiogenesis or cell cycle progression. As a standard systemic therapy option, it tremendously improves the survival of this devastating disease. Moreover, the combination of targeted therapy with immune checkpoint inhibitor (ICI) has demonstrated more potent anticancer effects and becomes the hot topic in clinical studies. The combining medications bring about a paradigm shift in the treatment of advanced HCC. In this review, we presented all approved targeted agents for advanced HCC with an emphasis on their clinical efficacy, summarized the advances of multi-target drugs in research for HCC and potential therapeutic targets for drug development. We also discussed the exciting results of the combination between targeted therapy and ICI.
Highlights
Hepatocellular carcinoma (HCC) accounts for approximately 75%-85% of all primary liver cancer [1]
In phase III studies, for MET-high advanced HCC patients who previously treated with sorafenib, no significantly improved progression-free survival (PFS) and overall survival (OS) were observed in tivantinib arm compared to the placebo arm [94, 95]
A clinical study reported that advanced HCC patients treated with the antiVEGFR2 mAb ramucirumab plus the anti-MET mAb emibetuzumab showed an 6.7% overall response rate, 60% DCR and 5.42 months PFS, which further supporting the results of preclinical study [98]
Summary
Hepatocellular carcinoma (HCC) accounts for approximately 75%-85% of all primary liver cancer [1]. RTK consists of an extracellular domain that binds specific ligand, a transmembrane domain and an intracellular domain with tyrosine kinase activity [21]. The binding of RTK to its ligand phosphorylates tyrosine residues of target protein and regulates a series of biochemical processes through corresponding downstream signaling pathways [17, 18]. The emergence of tyrosine kinase inhibitors (TKIs) has become a promising targeted therapeutic strategy [24, 25]. The emergence of targeted therapy has transformed the therapeutic landscape of advanced HCC [5, 24, 26,27,28]. Recent studies have shown that combinations of multiple therapeutic regimens demonstrated superior efficacy to monotherapy, combination of targeted therapy with immune checkpoint inhibitor (ICI) [32]. This review focused on the advances of targeted therapy for advanced HCC
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