Biomaterial Database

Modulation of Notch signaling as a therapeutic approach for liver cancer. 2015

Guang Wu, and George Wilson, and Jacob George, and Liang Qiao

Notch signaling is an evolutionarily conserved pathway crucial for the development and homeostasis of many organs including liver. Aberrant Notch signaling has been mechanistically linked to cancer development including liver cancer. The two principal types of liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). HCCs comprise over 80% of all liver cancers and are the 6(th) most common malignancy worldwide. Hepatocellular carcinoma is also a cancer with an extremely poor prognosis, being the 3(rd) commonest cause of cancer-related mortality. Accumulating evidence indicates that the role of Notch signaling in liver cancer is more complex than once thought and is dependent on the expression of specific Notch signaling components and the complex crosstalk with other signaling pathways. Currently there are a variety of gene therapy based approaches used to target Notch signaling in preclinical studies to successfully treat liver cancer including neutralizing antibodies, siRNA, shRNA and miRNA. The use of targeted anti-Notch therapy in the clinic to treat liver cancer will require considerable refinement of our current knowledge on the regulation of Notch signaling components and their effects in both normal and malignant liver cells in order to target specific Notch subunits which are critical to liver cancer tumorigenesis but not to the homeostasis of normal cells. Using this approach will reduce the major side effects, which are frequently seen in patients treated with GSIs to inhibit the entire Notch signaling pathway. Here our understanding of Notch signaling is reviewed, highlighting its function in liver cancer initiation, progress and opportunities for liver cancer therapies.

UI	MeSH Term	Description	Entries
D008113	Liver Neoplasms	Tumors or cancer of the LIVER.	Cancer of Liver,Hepatic Cancer,Liver Cancer,Cancer of the Liver,Cancer, Hepatocellular,Hepatic Neoplasms,Hepatocellular Cancer,Neoplasms, Hepatic,Neoplasms, Liver,Cancer, Hepatic,Cancer, Liver,Cancers, Hepatic,Cancers, Hepatocellular,Cancers, Liver,Hepatic Cancers,Hepatic Neoplasm,Hepatocellular Cancers,Liver Cancers,Liver Neoplasm,Neoplasm, Hepatic,Neoplasm, Liver
D006528	Carcinoma, Hepatocellular	A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.	Hepatocellular Carcinoma,Hepatoma,Liver Cancer, Adult,Liver Cell Carcinoma,Liver Cell Carcinoma, Adult,Adult Liver Cancer,Adult Liver Cancers,Cancer, Adult Liver,Cancers, Adult Liver,Carcinoma, Liver Cell,Carcinomas, Hepatocellular,Carcinomas, Liver Cell,Cell Carcinoma, Liver,Cell Carcinomas, Liver,Hepatocellular Carcinomas,Hepatomas,Liver Cancers, Adult,Liver Cell Carcinomas
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015316	Genetic Therapy	Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.	Gene Therapy,Somatic Gene Therapy,DNA Therapy,Gene Therapy, Somatic,Genetic Therapy, Gametic,Genetic Therapy, Somatic,Therapy, DNA,Therapy, Gene,Therapy, Somatic Gene,Gametic Genetic Therapies,Gametic Genetic Therapy,Genetic Therapies,Genetic Therapies, Gametic,Genetic Therapies, Somatic,Somatic Genetic Therapies,Somatic Genetic Therapy,Therapies, Gametic Genetic,Therapies, Genetic,Therapies, Somatic Genetic,Therapy, Gametic Genetic,Therapy, Genetic,Therapy, Somatic Genetic
D015972	Gene Expression Regulation, Neoplastic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.	Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D049109	Cell Proliferation	All of the processes involved in increasing CELL NUMBER including CELL DIVISION.	Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D051880	Receptors, Notch	A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN REPEATS in their cytoplasmic domains. The cytoplasmic domains are released upon ligand binding and translocate to the CELL NUCLEUS, where they act as transcription factors.	Notch Protein,Notch Receptor,Notch Receptors,Notch Proteins,Protein, Notch,Receptor, Notch
D058990	Molecular Targeted Therapy	Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease.	Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular
D018281	Cholangiocarcinoma	A malignant tumor arising from the epithelium of the BILE DUCTS.	Cholangiocellular Carcinoma,Extrahepatic Cholangiocarcinoma,Intrahepatic Cholangiocarcinoma,Carcinoma, Cholangiocellular,Carcinomas, Cholangiocellular,Cholangiocarcinoma, Extrahepatic,Cholangiocarcinoma, Intrahepatic,Cholangiocarcinomas,Cholangiocarcinomas, Extrahepatic,Cholangiocarcinomas, Intrahepatic,Cholangiocellular Carcinomas,Extrahepatic Cholangiocarcinomas,Intrahepatic Cholangiocarcinomas
D022781	Hepatocytes	The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.	Hepatic Cells,Cell, Hepatic,Cells, Hepatic,Hepatic Cell,Hepatocyte