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Review
. 2021 May 13:8:387-401.
doi: 10.2147/JHC.S300182. eCollection 2021.

Hepatocellular Carcinoma: An Overview of the Changing Landscape of Treatment Options

Andreas Koulouris  1 , Christos Tsagkaris  2 , Vasiliki Spyrou  3 , Eleni Pappa  4 , Aikaterini Troullinou  2 , Michail Nikolaou  5
Affiliations
Review

Hepatocellular Carcinoma: An Overview of the Changing Landscape of Treatment Options

Andreas Koulouris et al. J Hepatocell Carcinoma. .

Abstract

The last three years have seen remarkable progress in comprehending predisposing factors and upgrading our treatment arsenal concerning hepatocellular carcinoma (HCC). Until recently, there were no means to withstand the progression of viral hepatitis-associated liver cirrhosis to HCC. A deeper understanding of the molecular mechanism of the disease, the use of biomarkers, and the follow-up, allowed us to realize that conventional chemotherapy failing to increase survival in patients with advanced HCC tends to be exiled from clinical practice. Multi-kinase inhibitors (TKIs) such as sorafenib, lenvatinib targeting mainly the vascular endothelial growth factor receptors 1-3 VEGFRs 1-3 provided until recently the standard of care for these patients, as first- or second-line treatment. Since May 2020, the atezolizumab plus bevacizumab combination (immunotherapy plus anti-VEGF) has become the new reference standard in first-line HCC treatment. Additionally, anti-programmed cell death protein 1 (anti-PD-1) immunotherapy can be used as a second-line treatment following first-line treatment's failure. Phase III clinical trials have recently suggested the efficacy of novel anti-angiogenic factors such as cabozantinib and ramucirumab as a second-line treatment option. With considerations about toxicity arising, clinical trials are investigating combinations of the aforementioned targeted therapies with immunotherapy as first-line treatment. This paper aims to perform a systematic review describing the evolving treatment options for HCC over the last decades, ranging from neoadjuvant treatment to systemic therapy of advanced-stage HCC. With the landscape of HCC treatment shifting towards novel agents the forming of a new therapeutic algorithm for HCC seems to be imperative.

Keywords: biomarkers; hepatocellular carcinoma; immunotherapy; targeted therapy; tyrosine kinase inhibitors.

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Conflict of interest statement

The authors declare that there is no conflicts of interest.

Figures

Figure 1
Figure 1
Treatment algorithm for HCC.,
Figure 2
Figure 2
HCC treatment timeline.,,,
Figure 3
Figure 3
Treatment regimens and their mechanisms of action. The Ras/Raf/MEK/ERK and PI3K/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases.,,
See this image and copyright information in PMC

References

    1. Akinyemiju T, Akinyemiju T, Abera S; Global Burden of Disease Liver Cancer Collaboration, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 3;2017:1683–1691. doi:10.1001/jamaoncol.2017.3055 - DOI - PMC - PubMed
    1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386. doi:10.1002/ijc.29210 - DOI - PubMed
    1. Ryerson AB, Eheman CR, Altekruse SF, et al. Annual report to the nation on the status of cancer, 1975–2012, featuring the increasing incidence of liver cancer. Cancer. 2016;122:1312. doi:10.1002/cncr.29936 - DOI - PMC - PubMed
    1. Quaglia A. Hepatocellular carcinoma: a review of diagnostic challenges for the pathologist. J Hepatocell Carcinoma. 2018;5:99. doi:10.2147/JHC.S159808 - DOI - PMC - PubMed
    1. Pennisi G, Celsa C, Giammanco A, et al. The burden of hepatocellular carcinoma in non-alcoholic fatty liver disease: screening issue and future perspectives. Int J Mol Sci. 2019;20(22):5613. doi:10.3390/ijms20225613 - DOI - PMC - PubMed