MET as a druggable target in solid tumors

Genetic alteration of receptor tyrosine kinase (RTK) family is common in solid tumors. While many changes such as overexpression, mutation, and amplification are found to be associated to poor prognosis, targeted therapy against RTKs has become a new avenue for cancer therapeutics which have shown clinical efficacy. Our research has been focused on evaluating the MET RTK as a druggable target in glioblastoma, the most malignant type of brain tumor. Using a transgenic mouse model, we demonstrated that overexpressing MET and its ligand hepatocyte growth factor (HGF) along with p53 inhibition in neonatal mouse brain induced de novo glioma initiation. Moreover, the tumor cells isolated from the mouse model showed glioma stem cell property and were sensitive to MET inhibitors. These results suggest that HGF/MET axis elicits a driving force in gliomagenesis and is a druggable target for treating glioblastoma and other types of solid tumors.