Twenty-two percent of advanced HCC harbored potentially druggable genetic alterations, and MET amplification was associated with complete tumor response in patients with advanced HCC treated by a specific MET inhibitor.
The hepatocyte growth factor receptor c-Met has been shown to play an important role in the pathogenesis of HCC, but the influence of c-Met expression on the clinical course of HCC remains to be fully elucidated.
Therefore, it is crucial to investigate the expression of C-MET and PD-L1, and their association with clinicopathologic factors, to facilitate the development of targeted treatments for HCC.
We assessed nine single nucleotide polymorphisms (SNPs) in the FGF1, FGF2, FGF receptor (FGFR)-2, Flt-1, and c-MET genes in 245 HCC patients and 483 chronic hepatitis B virus (HBV) carriers without HCC.
This study investigated "repurposed" [<sup>18</sup>F]FACBC for PET imaging of primary liver cancer such as hepatocellular carcinoma (HCC) in comparison with [<sup>11</sup>C]Met.
In sum, our findings reveal a novel regulatory signaling cascade, the HULC/miR-2052/MET axis, which could potentially be exploited for therapeutic benefits in the treatment of HCC.
We tested the effects of MET inhibitors tivantinib and capmatinib in the mouse hepatocellular carcinoma (HCC) cell line HCA-1 and in immune-competent and immunodeficient mice with subcutaneous tumors grown from this cell line.
GRN status negatively correlates with HCC prognosis, and positively correlates with hyperproliferation, dedifferentiation and HGF/MET pathway activation, suggesting that it contributes to a transcriptomic profile typical of the proliferative class of HCC.
Heat-stress induced MET and EGFR signalling is distinct from growth factor mediated signalling in HCC cells and MET inhibition enhances heat stress induced HCC cell killing via a PI3K/AKT/mTOR-independent mechanism.
Immunohistochemical analysis was used to measure the expression of hepatocyte growth factor receptor (c-Met), β-catenin and focal adhesion kinase (FAK) in patients with HCC. c-Met expression was identified to be high in patients with larger tumors, higher α-fetoprotein (AFP) levels, higher Edmondson grades, portal vein invasion and higher tumor-node-metastasis (TNM) stages.
We explored the contribution of MET pathway to the enhanced HCC invasion and metastasis by VEGF signaling inhibition, and investigated the antitumor effects of NZ001, a novel dual inhibitor of MET and VEGFR2, in HCC.
Tivantinib did not improve overall survival compared with placebo in patients with MET-high advanced hepatocellular carcinoma previously treated with sorafenib.
Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease.
MicroRNA-206 prevents the pathogenesis of hepatocellular carcinoma by modulating expression of met proto-oncogene and cyclin-dependent kinase 6 in mice.
The expression in HA was variable and differed between molecular subtypes of this neoplasm: inflammatory and HNF1A mutation-associated type are characterized by overexpression of c-MET to an extent comparable with poorly-differentiated HCC, whereas Wnt/β-catenin dysfunction-associated type lacks overexpression, and the amount of c-MET protein accumulated in its cells is similar to the levels in non-neoplastic tissue and well- to moderately-differentiated HCC.
Taken together, it can be anticipated that more effective and safer c-Met targeting strategies for preventing HCC progression can be established in the future.
On the contrary, another lead is to study target a specific TKI such as c-MET inhibitors or TGFβR inhibitors in HCC sub-populations with promising results in early phase trials.
The ARQ 197-215 study randomized patients to tivantinib or placebo and pre-specified efficacy analyses indicated the predictive value of MET expression as a marker of benefit from tivantinib in hepatocellular carcinoma (HCC).