Fig. 1.

The MAPK pathway. Following activation of growth factor receptors by their ligands, signal transduction through the Ras-Raf-MEK-MAPK pathway occurs. With the help of Myc and CREB, signals are passed on to the nucleus and lead to transcription of genes that are relevant in proliferation and tumorigenesis. BRAF inhibition tackles signal transduction from Raf to MEK, whereas further downstream, MEK inhibition stops signal transduction from MEK to MAPK, thus counteracting resistance mechanisms that bypass Raf inhibition. L, ligand of growth factor receptor; GF-R, growth factor receptor; BI, BRAF inhibitor; MI, MEK inhibitor; CREB, cAMP response element-binding protein.