Figure 1.

Role of the mitogen activated protein kinase (MAPK) pathway in melanoma cells and targets of BRAF and MEK inhibitors. In normal cells, external growth stimuli trigger receptor tyrosine kinase (RTK), activating the MAPK pathway kinase cascade. In BRAF-driven melanoma, mutant BRAF (BRAF V600E) can start signaling independently of growth factor signal to hyperactivate cellular growth. BRAF mutated melanoma responds to BRAF/MEK inhibitors-targeted therapy. However, various intrinsic or adaptive resistance mechanisms attenuate response to targeted BRAF inactivation, deregulating signaling and rewiring cell metabolism.