Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3695
Peer-review started: May 4, 2018
First decision: May 16, 2018
Revised: June 28, 2018
Accepted: July 16, 2018
Article in press: July 16, 2018
Published online: September 7, 2018
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.
Core tip: Hepatocellular carcinoma (HCC) is a tumor usually arising from previous hepatic diseases as cirrhosis and chronic hepatitis B and C infections. Several studies have shown that a key factor for HCC oncogenesis is chronic inflammation. Inflammation induces changes in the gene expression pattern in surrounding cells. These changes provide an environment with a high level of cytokines, promoting hepatocyte transformation to tumor cells. New therapies against HCC are focused on regulating stromal cells within the tumor microenvironment to avoid HCC progression.