Submit to Cancers Review for Cancers Propose a Special Issue

Journal Browser

► Journal Browser

Molecular Mechanisms Involved in Hepatocarcinogenesis

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 27463

Share This Special Issue

Special Issue Editor

Dr. Hiroyuki Tsuchiya

E-Mail Website
Guest Editor

Division of Medical Genetics and Regenerative Medicine, Faculty of Medicine, Tottori University, Japan
Interests: hepatocellular carcinoma, cancer stem cells, hepatocarcinogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Primary liver cancer, mainly consisting of hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is a leading cause of cancer death worldwide. Recent advances in the development of multi-kinase inhibitors for the treatment of hepatocellular carcinoma have brought us closer than ever to enable the control or even the cure of liver cancer with systemic therapy. However, although it is well described that alcohol abuse, metabolic disturbances, and infection with hepatitis viruses are major pathogenic causes of hepatocarcinogenesis, it is still necessary to deepen our understanding of their molecular mechanisms, such as prevalent genomic alterations and affected signaling pathways. In addition, accumulating evidence indicates that there are additional factors that need to be considered, such as cancer stem cells and tumor microenvironment. These factors can also be involved in liver cancer recurrence. In order to develop more efficient drugs and to improve current therapies, it is necessary to identify previously unrecognized potential therapeutic targets by studying the hepatocarcinogenic process. This Special Issue covers research on molecular mechanisms underlying the development of liver cancer from the viewpoints of prevention and therapy.

Dr. Hiroyuki Tsuchiya
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hepatocellular carcinoma/cholangiocarcinoma
hepatocarcinogenic signaling/mutation
cancer stem cells
tumor microenvironment
viral, alcoholic, and non-alcoholic hepatitis
risk factors
recurrence

Published Papers (6 papers)

Download All Papers

Research

Jump to: Review

18 pages, 3856 KiB

Open AccessArticle

Broad Transcriptomic Impact of Sorafenib and Its Relation to the Antitumoral Properties in Liver Cancer Cells

by Laura Contreras, Alfonso Rodríguez-Gil, Jordi Muntané and Jesús de la Cruz

Cancers 2022, 14(5), 1204; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051204 - 25 Feb 2022

Cited by 1 | Viewed by 2429

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent and essentially incurable cancers in its advanced stages. The tyrosine kinase inhibitor Sorafenib (Sfb) remains the globally accepted treatment for advanced HCC. However, the extent of its therapeutic benefit is limited. Sfb exerts antitumor activity through its cytotoxic, anti-proliferative and pro-apoptotic roles in HCC cells. To better understand the molecular mechanisms underlying these effects, we used RNA sequencing to generate comprehensive transcriptome profiles of HepG2 and SNU423, hepatoblastoma- (HB) and HCC-derived cell lines, respectively, following a Sfb treatment at a pharmacological dose. This resulted in similar alterations of gene expression in both cell lines. Genes functionally related to membrane trafficking, stress-responsible and unfolded protein responses, circadian clock and activation of apoptosis were predominantly upregulated, while genes involved in cell growth and cycle, DNA replication and repair, ribosome biogenesis, translation initiation and proteostasis were downregulated. Our results suggest that Sfb causes primary effects on cellular stress that lead to upregulation of selective responses to compensate for its negative effect and restore homeostasis. No significant differences were found specifically affecting each cell line, indicating the robustness of the Sfb mechanism of action despite the heterogeneity of liver cancer. We discuss our results on terms of providing rationalization for possible strategies to improve Sfb clinical outcomes. Full article

(This article belongs to the Special Issue Molecular Mechanisms Involved in Hepatocarcinogenesis)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 2895 KiB

Open AccessEditor’s ChoiceReview

Innate and Adaptive Immunopathogeneses in Viral Hepatitis; Crucial Determinants of Hepatocellular Carcinoma

by Marco Y. W. Zaki, Ahmed M. Fathi, Samara Samir, Nardeen Eldafashi, Kerolis Y. William, Maiiada Hassan Nazmy, Moustafa Fathy, Upkar S. Gill and Shishir Shetty

Cancers 2022, 14(5), 1255; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14051255 - 28 Feb 2022

Cited by 23 | Viewed by 4161

Abstract

Viral hepatitis B (HBV) and hepatitis C (HCV) infections remain the most common risk factors for the development of hepatocellular carcinoma (HCC), and their heterogeneous distribution influences the global prevalence of this common type of liver cancer. Typical hepatitis infection elicits various immune responses within the liver microenvironment, and viral persistence induces chronic liver inflammation and carcinogenesis. HBV is directly mutagenic but can also cause low-grade liver inflammation characterized by episodes of intermittent high-grade liver inflammation, liver fibrosis, and cirrhosis, which can progress to decompensated liver disease and HCC. Equally, the absence of key innate and adaptive immune responses in chronic HCV infection dampens viral eradication and induces an exhausted and immunosuppressive liver niche that favors HCC development and progression. The objectives of this review are to (i) discuss the epidemiological pattern of HBV and HCV infections, (ii) understand the host immune response to acute and chronic viral hepatitis, and (iii) explore the link between this diseased immune environment and the development and progression of HCC in preclinical models and HCC patients. Full article

(This article belongs to the Special Issue Molecular Mechanisms Involved in Hepatocarcinogenesis)

► Show Figures

Figure 1

36 pages, 2315 KiB

Open AccessReview

The Bright and the Dark Side of TGF-β Signaling in Hepatocellular Carcinoma: Mechanisms, Dysregulation, and Therapeutic Implications

by Medine Zeynep Gungor, Merve Uysal and Serif Senturk

Cancers 2022, 14(4), 940; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14040940 - 14 Feb 2022

Cited by 15 | Viewed by 5278

Abstract

Hepatocellular carcinoma (HCC) is associated with genetic and nongenetic aberrations that impact multiple genes and pathways, including the frequently dysregulated transforming growth factor β (TGF-β) signaling pathway. The regulatory cytokine TGF-β and its signaling effectors govern a broad spectrum of spatiotemporally regulated molecular and cellular responses, yet paradoxically have dual and opposing roles in HCC progression. In the early stages of tumorigenesis, TGF-β signaling enforces profound tumor-suppressive effects, primarily by inducing cell cycle arrest, cellular senescence, autophagy, and apoptosis. However, as the tumor advances in malignant progression, TGF-β functionally switches to a pro-tumorigenic signal, eliciting aggressive tumor traits, such as epithelial–mesenchymal transition, tumor microenvironment remodeling, and immune evasion of cancer cells. On this account, the inhibition of TGF-β signaling is recognized as a promising therapeutic strategy for advanced HCC. In this review, we evaluate the functions and mechanisms of TGF-β signaling and relate its complex and pleiotropic biology to HCC pathophysiology, attempting to provide a detailed perspective on the molecular determinants underlying its functional diversion. We also address the therapeutic implications of the dichotomous nature of TGF-β signaling and highlight the rationale for targeting this pathway for HCC treatment, alone or in combination with other agents. Full article

(This article belongs to the Special Issue Molecular Mechanisms Involved in Hepatocarcinogenesis)

► Show Figures

Figure 1

22 pages, 1180 KiB

Open AccessReview

Hepatocellular Carcinoma: Molecular Pathogenesis and Therapeutic Advances

by Blanca Cucarull, Anna Tutusaus, Patricia Rider, Tania Hernáez-Alsina, Carlos Cuño, Pablo García de Frutos, Anna Colell, Montserrat Marí and Albert Morales

Cancers 2022, 14(3), 621; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030621 - 26 Jan 2022

Cited by 31 | Viewed by 7845

Abstract

Hepatocellular carcinoma (HCC), the most common form of liver cancer, continues to be a serious medical problem with poor prognosis, without major therapeutic improvement for years and increasing incidence. Fortunately, advances in systemic treatment options are finally arriving for HCC patients. After a decade of sorafenib as a standard therapy for advanced HCC, several tyrosine kinase inhibitors (TKIs), antiangiogenic antibodies, and immune checkpoint inhibitors have reached the clinic. Although infections by hepatitis B virus and hepatitis C virus remain principal factors for HCC development, the rise of non- alcoholic steatohepatitis from diabetes mellitus or metabolic syndrome is impeding HCC decline. Knowledge of specific molecular mechanisms, based on the etiology and the HCC microenvironment that influence tumor growth and immune control, will be crucial for physician decision-making among a variety of drugs to prescribe. In addition, markers of treatment efficacy are needed to speed the movement of patients towards other potentially effective treatments. Consequently, research to provide scientific data for the evidence-based management of liver cancer is guaranteed in the coming years and discussed here. Full article

(This article belongs to the Special Issue Molecular Mechanisms Involved in Hepatocarcinogenesis)

► Show Figures

Figure 1

16 pages, 1082 KiB

Open AccessReview

The Emerging Influences of Alpha-Fetoprotein in the Tumorigenesis and Progression of Hepatocellular Carcinoma

by Ye Xu, Qinglong Guo and Libin Wei

Cancers 2021, 13(20), 5096; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13205096 - 12 Oct 2021

Cited by 13 | Viewed by 3827

Abstract

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide, and its mortality rate is the third-highest, after lung cancer and colorectal cancer. Currently, systematic targeted therapies for HCC mainly include multiple kinase inhibitors and immunotherapy. However, these drugs carry a black-box warning about the potential for inducing severe toxicity, and they do not significantly prolong the survival period of patients due to the highly heterogeneous characteristics of HCC etiology. In order to improve the prediction, effective treatment and prognosis of HCC, the tools and different biomarkers in clinical practices are recommended. Alpha-fetoprotein (AFP) is the earliest and the most widely used serum marker in the detection of HCC. Interestingly, serum AFP and cytoplasmic AFP show different, even opposite, roles in the cancer progression of HCC. This review focuses on biological characteristics, regulatory mechanisms for gene expression, emerging influences of AFP in HCC and its possible implications in HCC-targeted therapy. Full article

(This article belongs to the Special Issue Molecular Mechanisms Involved in Hepatocarcinogenesis)

► Show Figures

Figure 1

16 pages, 775 KiB

Open AccessReview

Epigenetic Changes Affecting the Development of Hepatocellular Carcinoma

by Ewa Wolinska and Maciej Skrzypczak

Cancers 2021, 13(16), 4237; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13164237 - 23 Aug 2021

Cited by 12 | Viewed by 3108

Abstract

Hepatocellular carcinoma (HCC) remains a serious oncologic issue with still a dismal prognosis. So far, no key molecular mechanism that underlies its pathogenesis has been identified. Recently, by specific molecular approaches, many genetic and epigenetic changes arising during HCC pathogenesis were detected. Epigenetic studies revealed modified methylation patterns in HCC tumors, dysfunction of enzymes engaged in the DNA methylation process, and a set of histone modifications that influence gene expression. HCC cells are also influenced by the disrupted function of non-coding RNAs, such as micro RNAs and long non-coding RNAs. Moreover, a role of liver cancer stem cells in HCC development is becoming evident. The reversibility of epigenetic changes offers the possibility of influencing them and regulating their undesirable effects. All these data can be used not only to identify new therapeutic targets but also to predict treatment response. This review focuses on epigenetic changes in hepatocellular carcinoma and their possible implications in HCC therapy. Full article

(This article belongs to the Special Issue Molecular Mechanisms Involved in Hepatocarcinogenesis)

► Show Figures