Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 May 31:14:1163967.
doi: 10.3389/fimmu.2023.1163967. eCollection 2023.

The multikinase inhibitor axitinib in the treatment of advanced hepatocellular carcinoma: the current clinical applications and the molecular mechanisms

Hao Jiang  1 , Jian Liao  2 , Liezhi Wang  1 , Chong Jin  1 , Jinggang Mo  1 , Sheng Xiang  3
Affiliations
Review

The multikinase inhibitor axitinib in the treatment of advanced hepatocellular carcinoma: the current clinical applications and the molecular mechanisms

Hao Jiang et al. Front Immunol. .

Abstract

Advanced hepatocellular carcinoma (HCC) is a formidable public health problem with limited curable treatment options. Axitinib, an oral tyrosine kinase inhibitor, is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3. This anti-angiogenic drug was found to have promising activity in various solid tumors, including advanced HCC. At present, however, there is no relevant review article that summarizes the exact roles of axitinib in advanced HCC. In this review, 24 eligible studies (seven studies in the ClinicalTrials, eight experimental studies, and nine clinical trials) were included for further evaluation. The included randomized or single-arm phase II trials indicated that axitinib could not prolong the overall survival compared to the placebo for the treatment of advanced HCC, but improvements in progression free survival and time to tumor progression were observed. Experimental studies showed that the biochemical effects of axitinib in HCC might be regulated by its associated genes and affected signaling cascades (e.g. VEGFR2/PAK1, CYP1A2, CaMKII/ERK, Akt/mTor, and miR-509-3p/PDGFRA). FDA approved sorafenib combined with nivolumab (an inhibitor of PD-1/PD-L1) as the first line regimen for the treatment of advanced HCC. Since both axitinib and sorafenib are tyrosine kinase inhibitors as well as the VEGFR inhibitors, axitinib combined with anti-PDL-1/PD-1 antibodies may also exhibit tremendous potential in anti-tumoral effects for advanced HCC. The present review highlights the current clinical applications and the molecular mechanisms of axitinib in advanced HCC. To move toward clinical applications by combining axitinib and other treatments in advanced HCC, more studies are still warranted in the near future.

Keywords: axitinib; hepatocellular carcinoma; mechanism; survival; tyrosine kinase.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The molecular mechanism underlying the roles of axitinib in advanced HCC.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin (2021) 71:209–49. doi: 10.3322/caac.21660 - DOI - PubMed
    1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin (2023) 73:17–48. doi: 10.3322/caac.21763 - DOI - PubMed
    1. McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis (2015) 19:223–38. doi: 10.1016/j.cld.2015.01.001 - DOI - PMC - PubMed
    1. Nischalke HD, Berger C, Luda C, Berg T, Muller T, Grunhage F, et al. . The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis c cirrhosis. PloS One (2011) 6:e27087. doi: 10.1371/journal.pone.0027087 - DOI - PMC - PubMed
    1. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. . Hepatocellular carcinoma. Nat Rev Dis Primers (2021) 7:6. doi: 10.1038/s41572-020-00240-3 - DOI - PubMed

Publication types

MeSH terms