García-Vilas, Javier AMedina, Miguel Ángel2023-01-252023-01-252018http://hdl.handle.net/10668/12926Hepatocellular 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.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/Hepatocellular carcinomaHepatocyte growth factor/c-METTumor microenvironmentc-Met canonical and non-canonical pathwaysAntineoplastic AgentsCarcinoma, HepatocellularCell MovementCell ProliferationCell Transformation, NeoplasticEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHepatocyte Growth FactorHepatocytesHumansLiver NeoplasmsMicroRNAsNeovascularization, PathologicOxidative StressProto-Oncogene Proteins c-metSignal TransductionTumor Microenvironmentresearch article30197476open access10.3748/wjg.v24.i33.36952219-2840PMC6127652https://doi.org/10.3748/wjg.v24.i33.3695https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127652/pdf