Emerging Raf inhibitors

Background: The Ras/Raf/MEK/ERK pathway is often activated by geneticalterations in upstream signaling molecules. Integral components of thispathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/MEK/ERK pathway has profound effects on proliferative, apoptotic anddifferentiation pathways. This pathway can often be effectively silencedby MEK inhibitors. Objectives/methods: This review discusses targeting ofMEK which could lead to novel methods of controlling abnormal proliferationthat arises in cancer and other proliferative diseases. The importantroles that genetics play in response of patients to MEK inhibitors is alsoevaluated in this review. This review also discusses the potential of combiningMEK inhibitors with other types of therapy (e.g., other signal transductioninhibitors, chemo- and radiotherapy). Finally, we examine novel usesof these inhibitors such as in prevention of cellular aging and the developmentof cancer stem cells. Results/conclusions: Targeting MEK has beenshown to be effective in suppressing many important pathways involvedin cell growth and the prevention of apoptosis. MEK inhibitors have manypotential therapeutic uses in suppression of cancer, proliferative diseasesas well as aging.