Figure 1.

Here, the major downstream signaling pathways of HGF/c-MET and targets of trametinib are shown. MET triggers several downstream signaling pathways: the Ras pathway, the PI3K–Akt pathway, and the STAT3 pathway. Trametinib targets the Ras (Ras/Raf/MEK/ERK, MAPK) pathway in various malignancies. HGF, hepatocyte growth factor; SHP2, SH2 domain-containing tyrosine phosphatase 2; SHC, SH2 domain-containing transforming protein; GRB2, growth factor receptor-bound protein 2; SOS, son of sevenless; MEK, mitogen-activated protein kinase kinase; ERK, extracellular signal-regulated kinases; PI3K, Phosphoinositide 3-kinase; Akt, protein kinase B; BAD, BCL-2 antagonist of cell death; MDM2, murine double minute 2; STAT3, Signal transducer and activator of transcription 3.