Updates on the hepatocyte growth factor/c-Met axis in hepatocellular carcinoma and its therapeutic implications.
Hepatocellular carcinoma (HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor (HGF)/c-mesenchymal-epithelial transition rec...
| Autores: | , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/25237 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/25237 |
| Access Level: | acceso abierto |
| Palabra clave: | Hepatocellular carcinoma Hepatocyte growth factor/c-MET Tumor microenvironment c-Met canonical and non-canonical pathways Antineoplastic Agents Carcinoma, Hepatocellular Cell Movement Cell Proliferation Cell Transformation, Neoplastic Epithelial-Mesenchymal Transition Gene Expression Regulation, Neoplastic Hepatocyte Growth Factor Hepatocytes Humans Liver Neoplasms MicroRNAs Neovascularization, Pathologic Oxidative Stress Proto-Oncogene Proteins c-met Signal Transduction Tumor Microenvironment |
| Sumario: | Hepatocellular carcinoma (HCC) is the fifth most common cancer and is the second leading cause of cancer death. Since the diagnosis of HCC is difficult, in many cases patients with HCC are diagnosed advanced stage of development. Hepatocyte growth factor (HGF)/c-mesenchymal-epithelial transition receptor (c-Met) axis is a key signaling pathway in HCC, either via canonical or non-canonical pathways. Available treatments against HCC based upon HGF/c-Met inhibition can increase patient lifespan, but do not reach the expected therapeutic benefits. In HCC, c-Met monomers can bind other receptor monomers, activating several noncanonical signaling pathways, leading to increased cell proliferation, invasion, motility, and drug resistance. All of these processes are enhanced by the tumor microenvironment, with stromal cells contributing to boost tumor progression through oxidative stress, angiogenesis, lymphangiogenesis, inflammation, and fibrosis. Novel treatments against HCC are being explored to modulate other targets such as microRNAs, methyltransferases, and acetyltransferases, which are all involved in the regulation of gene expression in cancer. This review compiles basic knowledge regarding signaling pathways in HCC, and compounds already used or showing potential to be used in clinical trials. |
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