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
. 2019 May 21;25(19):2279-2293.
doi: 10.3748/wjg.v25.i19.2279.

Mechanisms of hepatocellular carcinoma progression

Affiliations
Review

Mechanisms of hepatocellular carcinoma progression

Olorunseun O Ogunwobi et al. World J Gastroenterol. .

Abstract

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells, immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.

Keywords: Alcohol consumption; Cancer stem cells; Circulating tumor cells; Epithelial-mesenchymal transition; Hepatocellular carcinoma; Immunomodulation; Neural regulation; Tumor microenvironment; Tumor-stromal interactions; Viral/non-viral hepatitis.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: Ogunwobi OO, Tan Y and Ma GX are supported by the National Cancer Institute grant number U54 CA221704(5). Ogunwobi OO is a Co-Founder of NucleoBio, Inc, a City University of New York biotechnology start-up company.

Figures

Figure 1
Figure 1
Summary of the HCC progression mechanisms discussed in this review. HCC: Hepatocellular carcinoma; HBV: Hepatitis B virus; HCV: Hepatitis C virus.
Figure 2
Figure 2
Use of circulating tumor cells as a non-invasive means to study HCC progression. CTCs: Circulating tumor cells; HCC: Hepatocellular carcinoma.

Similar articles

Cited by

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7–30. - PubMed
    1. Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1. - PMC - PubMed
    1. Golabi P, Fazel S, Otgonsuren M, Sayiner M, Locklear CT, Younossi ZM. Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities. Medicine (Baltimore) 2017;96:e5904. - PMC - PubMed
    1. Medavaram S, Zhang Y. Emerging therapies in advanced hepatocellular carcinoma. Exp Hematol Oncol. 2018;7:17. - PMC - PubMed