Hepatocellular Carcinoma: From Molecular Basis to Novel...
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Editorial Hepatocellular Carcinoma: From Molecular Basis to Novel Treatment Approaches Hikmet AkkJz Professor of Gastroenterology and Hepatology, Head of Gastroenterology and Hepatology, C ¸ ukurova University, Turkey Correspondence should be addressed to Hikmet Akkız; [email protected] Received 20 December 2018; Accepted 31 December 2018; Published 3 March 2019 Copyright © Hikmet Akkız. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Hepatocellular carcinoma (HCC) is among the most preva- lent and lethal cancers in the world and is the fih most common cancer and the second leading cause of cancer- related deaths. HCC incidence has increased dramatically during the last decade worldwide. HCC is endemic in East Asia and sub-Saharan Africa where the major risk factors are hepatitis B virus (HBV) and hepatitis C Virus (HCV) infection. Aflatoxin B is a relevant cofactor for HCC in sub- Saharan Africa. In the United States and Western Europe, Nonalcoholic Steatohepatitis is an emerging risk factor for the development of HCC. Recently, Genome-Wide Association Study (GWAS) and Next Generation Sequencing (NGS) technologies have sig- nificantly improved our understanding of the molecular pathogenesis of HCC. Hepatocarcinogenesis is driven by interaction between host genetic polymorphisms, environ- mental factors including metabolic syndrome, aflatoxin B, alcohol consumption, and viral factors including HBV and HCV infection. Key molecular drivers involved in hepatocar- cinogenesis have been demonstrated. Molecular alterations at genomic, transcriptomic, and epigenomic level have been shown to be drivers in hepatocarcinogenesis. Genomic insta- bility is key driver in hepatocarcinogenesis that may result in copy number alterations and somatic mutations. Epigenomic alterations causing DNA mutilation, histone modification, and chromatin remodeling regulate gene expression at the genome. Telomere and Telomerase have a key role in HCC development. Telomerase reverse transcriptase promoter (TERT) mutation is an early somatic alteration in hepatocar- cinogenesis. Telomerase reactivation occurs in approximately % of HCC patients due to TERT promoter mutation, TERT amplification, and HBV insertion into the TERT promoter. Inactivation of p pathway, alterations in cell cycle signaling pathway, activation of Wnt/B-Catenin signaling and oxidative stress pathways, epigenetic alterations causing chromatin remodeling, and activation of Akt-mTOR-MAPK signaling have been shown to promote HCC progression. Barcelona Clinic Liver Cancer (BCLC) staging system is the most used staging system in the world for estimating the prognosis of HCC patients and contributes to clinicians choice of an evidence-based allocation of curative and pallia- tive treatments. According to BCLC staging system, potential curative treatments such as ablation, hepatic resection, and liver transplantation are standard options in stage and A HCC patients. Although BCLC A stage is quite specific, BCLC stage B HCC (intermediate stage) is characterized by high heterogeneity which shows a significant challenge in terms of determining the most effective therapy. BCLC staging system recommends transarterial chemoemboliza- tion (TACE) for BCLC B patients. However, potential curative treatments may provide more favorable clinical outcomes in some BCLC B patients with preserved liver function. e advanced stage HCC (BCLC C) includes an extreme- ly heterogeneous patient population characterized by extra- hepatic metastasis, macrovascular invasion, a wide range of Child-Pugh scores (A-B), and Eastern Cooperative Oncology Group performance status (PS -) and systemic therapy with the multikinase inhibitor, sorafenib, being rec- ommended in patients with advanced stage HCC. is special issue includes relevant research articles and review articles. In the review article titled “Pleiotropic Effects of Heparins: From Clinical Applications to Molecular Mechanisms in Hepatocellular Carcinoma” published by P. Korhan et al., the authors summarize the state of knowledge whereby heparin may crosstalk with molecules playing a role in hepatocarcinogenesis, and highlight new experimental and Hindawi Canadian Journal of Gastroenterology and Hepatology Volume 2019, Article ID 4970731, 2 pages https://doi.org/10.1155/2019/4970731
Transcript of Hepatocellular Carcinoma: From Molecular Basis to Novel...
EditorialHepatocellular Carcinoma: From Molecular Basis to NovelTreatment Approaches
Hikmet AkkJz
Professor of Gastroenterology and Hepatology, Head of Gastroenterology and Hepatology, Cukurova University, Turkey
Correspondence should be addressed to Hikmet Akkız; [email protected]
Received 20 December 2018; Accepted 31 December 2018; Published 3 March 2019
Copyright © 2019 Hikmet Akkız.�is is an open access article distributed under theCreative Commons Attribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Hepatocellular carcinoma (HCC) is among the most preva-lent and lethal cancers in the world and is the fih mostcommon cancer and the second leading cause of cancer-related deaths. HCC incidence has increased dramaticallyduring the last decade worldwide. HCC is endemic in EastAsia and sub-Saharan Africa where the major risk factorsare hepatitis B virus (HBV) and hepatitis C Virus (HCV)infection. Aflatoxin B1 is a relevant cofactor for HCC in sub-Saharan Africa. In the United States and Western Europe,Nonalcoholic Steatohepatitis is an emerging risk factor for thedevelopment of HCC.
Recently, Genome-Wide Association Study (GWAS) andNext Generation Sequencing (NGS) technologies have sig-nificantly improved our understanding of the molecularpathogenesis of HCC. Hepatocarcinogenesis is driven byinteraction between host genetic polymorphisms, environ-mental factors including metabolic syndrome, aflatoxin B1,alcohol consumption, and viral factors including HBV andHCV infection. Keymolecular drivers involved in hepatocar-cinogenesis have been demonstrated. Molecular alterationsat genomic, transcriptomic, and epigenomic level have beenshown to be drivers in hepatocarcinogenesis. Genomic insta-bility is key driver in hepatocarcinogenesis that may result incopy number alterations and somatic mutations. Epigenomicalterations causing DNA mutilation, histone modification,and chromatin remodeling regulate gene expression at thegenome. Telomere and Telomerase have a key role in HCCdevelopment. Telomerase reverse transcriptase promoter(TERT) mutation is an early somatic alteration in hepatocar-cinogenesis. Telomerase reactivation occurs in approximately90%ofHCCpatients due to TERT promotermutation, TERTamplification, and HBV insertion into the TERT promoter.Inactivation of p53 pathway, alterations in cell cycle signaling
pathway, activation ofWnt/B-Catenin signaling and oxidativestress pathways, epigenetic alterations causing chromatinremodeling, and activation of Akt-mTOR-MAPK signalinghave been shown to promote HCC progression.
Barcelona Clinic Liver Cancer (BCLC) staging system isthe most used staging system in the world for estimatingthe prognosis of HCC patients and contributes to clinicianschoice of an evidence-based allocation of curative and pallia-tive treatments. According to BCLC staging system, potentialcurative treatments such as ablation, hepatic resection, andliver transplantation are standard options in stage 0 andA HCC patients. Although BCLC A stage is quite specific,BCLC stage B HCC (intermediate stage) is characterizedby high heterogeneity which shows a significant challengein terms of determining the most effective therapy. BCLCstaging system recommends transarterial chemoemboliza-tion (TACE) for BCLCBpatients.However, potential curativetreatments may provide more favorable clinical outcomes insome BCLC B patients with preserved liver function.
�e advanced stage HCC (BCLCC) includes an extreme-ly heterogeneous patient population characterized by extra-hepatic metastasis, macrovascular invasion, a wide rangeof Child-Pugh scores (A5-B9), and Eastern CooperativeOncology Group performance status (PS 0-2) and systemictherapy with the multikinase inhibitor, sorafenib, being rec-ommended in patients with advanced stage HCC.
�is special issue includes relevant research articlesand review articles. In the review article titled “PleiotropicEffects of Heparins: From Clinical Applications to MolecularMechanisms in Hepatocellular Carcinoma” published by P.Korhan et al., the authors summarize the state of knowledgewhereby heparin may crosstalk with molecules playing a rolein hepatocarcinogenesis, and highlight new experimental and
HindawiCanadian Journal of Gastroenterology and HepatologyVolume 2019, Article ID 4970731, 2 pageshttps://doi.org/10.1155/2019/4970731
2 Canadian Journal of Gastroenterology and Hepatology
clinical research-related personalized therapy in patients withcancer at risk of thromboembolism.
�e research article published by G. Odabas et al. showedthat Plexin C1 distinguishes HCC cells of epithelial character-istics from those with the mesenchymal phenotype and HCCtissue overexpresses Plexin C1 compared to stroma.
In the review article titled “Molecular Pathogenesis ofNonalcoholic Steatohepatitis- (NASH-) Related Hepatocellu-lar Carcinoma” written by O. Kutlu et al., the investigatorsprovide comprehensive knowledge of NASH-related hepato-carcinogenesis and highlight molecular signaling pathwaysthat may have a role in HCC development.
H. Akkiz et al. have demonstrated the association be-tween portal vein thrombosis andmaximum tumor diameter,multifocality, and AFP in the large cohort study.
In the review article on local ablation therapies forHCC, S. Shiina et al. have given updated knowledge aboutvarious ablation techniques and compared them to surgicalmodalities.
Conflicts of Interest
�e editors declare that they have no conflicts of interestregarding the publication of this special issue.
Acknowledgments
Finally, I would like to knowledge the Guest Editors DR.Yaman Tokat, Dr. Brian Carr, Dr. Ali Canbay, and Dr.Shuichiro Shiina for valuable endeavours and contributions.Additionally, I would like to thank the Cukurova Universityfor financial support.
Hikmet Akkız
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