Emerging Raf inhibitors

Background: The Ras/Raf/MEK/ERK pathway is often activated by genetic alterations in upstream signaling molecules. Integral components of this pathway such as Ras and B-Raf are also activated by mutation. The Ras/Raf/ MEK/ERK pathway has profound effects on proliferative, apoptotic and differentiation pathways. This pathway can often be effectively silenced by MEK inhibitors. Objectives/methods: This review discusses targeting of MEK which could lead to novel methods of controlling abnormal proliferation that arises in cancer and other proliferative diseases. The important roles that genetics play in response of patients to MEK inhibitors is also evaluated in this review. This review also discusses the potential of combining MEK inhibitors with other types of therapy (e.g., other signal transduction inhibitors, chemo- and radiotherapy). Finally, we examine novel uses of these inhibitors such as in prevention of cellular aging and the development of cancer stem cells. Results/conclusions: Targeting MEK has been shown to be effective in suppressing many important pathways involved in cell growth and the prevention of apoptosis. MEK inhibitors have many potential therapeutic uses in suppression of cancer, proliferative diseases as well as aging.