Fig. 2

Targeting RAF–MEK–ERK signaling pathway. GTP-bounding RAS recruits and activates RAF, which in turn initiates a cascade of protein phosphorylation starting with MEK. Activated MEK phosphorylates ERK that moves from the cytoplasm to the nucleus where it phosphorylates several transcription factors. Mutational activation of RAF–MEK–ERK cascade contributes to progression of the disease. Selective inhibitors of MEK, e.g. trametinib, cause potent and durable suppression of ERK signaling