Targeting hepatocyte growth factor/c-mesenchymal-epithelial transition factor axis in hepatocellular carcinoma: Rationale and therapeutic strategies

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. The outcome of current standard treatments, as well as targeted therapies in advanced stages, are still unsatisfactory. Attention has been drawn to novel strategies for better treatment efficacy. Hepatocyte growth factor/c-mesenchymal-epithelial transition factor (HGF/c-Met) axis has been known as an essential element in the regulation of liver diseases and as an oncogenic factor in HCC. In this review, we collected the evidence of HGF/c-Met as a tumor progression and prognostic marker, discussed the anti-c-Met therapy in vitro, summarized the outcome of c-Met inhibitors in clinical trials, and identified potential impetus for future anti-c-Met treatments. We also analyzed the inconsistency of HGF/c-Met from various publications and offered reasonable explanations based on the current understanding in this area. In conclusion, HGF/c-Met plays a crucial role in the progression and growth of HCC, and the strategies to inhibit this pathway may facilitate the development of new and effective treatments for HCC patients.