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Mechanisms of hepatocellular carcinoma progression

World Journal of Gastroenterology 2019年第19期25卷 2279-2293页

作者： Olorunseun O Ogunwobi Trisheena Harricharran Jeannette Huaman Anna Galuza Oluwatoyin Odumuwagun Yin Tan Grace X Ma Minhhuyen T Nguyen Department of Biological Sciences Hunter College of The City University of New York The Graduate Center Departments of Biology and Biochemistry The City University of New York Joan and Sanford I. Weill Department of Medicine Weill Cornell Medicine Cornell University Hunter College Center for Cancer Health Disparities Research (CCHDR) Center for Asian Health School of Medicine Temple University Department of Medicine Fox Chase Cancer Center

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.

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

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