Advances of Targeted Therapy for Hepatocellular Carcinoma

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.

Focal adhesion kinase inhibitor TAE226 combined with Sorafenib slows down hepatocellular carcinoma by multiple epigenetic effects

“…The partial success of SOR has generated enthusiasm in the development of new molecules to be used as first- or second-line agents for systemic treatment of HCC. Between 2017 and 2018, four drugs (Lenvatinib, Regorafenib, Cabozantinib, and Ramucirumab), were found to be effective and tolerated, and have been approved by the Food and Drug Administration (FDA) as first- or second-line therapeutic agents for HCC patients [ 4 , 5 , 7 , 8 ]. To minimize resistance that often occurs as a consequence of the multi-step nature of HCC pathogenesis, the use of multi-target and/or combined therapies are suggested as the optimal strategy.…”

Exploring the mechanisms underlying the therapeutic effect of the Radix Bupleuri-Rhizoma Cyperi herb pair on hepatocellular carcinoma using multilevel data integration and molecular docking

“…Song et al [ 34 ] showed that reticulon 3-mediated activation of Chk2/p53 inhibit hepatocellular carcinogenesis. Moreover, some existing targeted therapies exert anti-HCC effects through specific signals, including anti-angiogenesis or cell cycle progression [ 35 ]. These results suggest that the pathological mechanism of HCC is very complex and involves the regulation of multiple genes and signaling pathways during progression.…”

Intraarterial Therapies for the Management of Hepatocellular Carcinoma

“…The use of systemic therapies in combination with transarterial embolization techniques is an area of significant clinical and research focus [ 232 ]. Some of the many targeted systemic therapies that have been studied include, but are not limited to, MAPK Inhibitors, including sunitinib, sorafenib, imatinib, cabozantinib, lenvatinib, and selumetinib [ 233 , 234 ]. Others include immunotherapeutic agents such as ipilimumab, nivolumab, and pembrolizumab [ 235 , 236 , 237 ].…”