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

Abstract

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.

LncRNA UCA1 mediates Cetuximab resistance in Colorectal Cancer via the MiR-495 and HGF/c-MET Pathways

“…Here, siRNA-mediated c-MET downregulation or PHA-665752-mediated c-MET tyrosine kinase activity inhibition prevented HGF-dependent activation of the PI3K/AKT and MAPK pathways and resensitized cells to cetuximab-induced growth-inhibitory effects. Many c-MET-targeting therapeutics, including TKIs, mAbs, and molecular decoys, are currently undergoing clinical development [62][63][64][65]. The efficacy and safety of combined receptor tyrosine kinase (RTK) therapy should be evaluated in vivo to overcome EGFR TKI resistance in the future.…”

CYP1A2 suppresses hepatocellular carcinoma through antagonizing HGF/MET signaling

“…Hyperactivation of hepatocyte growth factor/c-mesenchymal-epithelial transition factor (HGF/MET) signaling contributes to tumor formation, development, maintenance, and metastasis. In HCC, the expression of MET is increased in 25% to 80% patients 2 - 4 . Notably, a high amount of HGF and MET indicates poor differentiation and negative prognoses 5 , 6 .…”

Dioscorea Zingiberensis New Saponin Inhibits the Growth of Hepatocellular Carcinoma by Suppressing the Expression of Long Non-coding RNA TCONS-00026762

“…Hepatocellular carcinoma (HCC) is among top 10 cancers that exhibit high mortality rates worldwide. Over 840,000 new cases of HCC are reported and 780,000 people die of HCC annually ( Ferlay et al, 2015 ; Bray et al, 2018 ; Yu et al, 2021 ). Around the world, the leading cause of liver cancer is chronic viral hepatitis, namely hepatitis B and C. However, due to the increase in hepatitis B vaccination, studies have predicted that the rising incidence of alcohol consumption and obesity worldwide will overtake viral hepatitis as the most common cause of HCC ( Akinyemiju et al, 2017 ).…”