Figure 7. Schematic representation of the mechanisms of which statins overcome the apoptotic resistance to MEK inhibitors through the blockage of the mevalonate pathway.

Activated pathways are drawn with bold lines. Deactivated pathways are drawn with dotted lines. (A) MAPK pathway is dominantly activated to promote cell growth in untreated KRAS and/or BRAF mutated cancer cells. (B) MEK inhibition induces Akt activation and causes the apoptotic resistance to MEK inhibitors. (C) Blockage of the protein geranylgeranylation by statins suppresses Akt activation and thereby overcomes apoptotic resistance to MEK inhibitors.