Emerging MEK inhibitors

James A. McCubrey, Linda S. Steelman, Steven L. Abrams, William H. Chappell, Suzanne Russo, Roger Ove, Michele Milella, Agostino Tafuri, Paolo Lunghi, Antonio Bonati, Franca Stivala, Ferdinando Nicoletti, Massimo Libra, Alberto M. Martelli, Giuseppe Montalto, Melchiorre Cervello

Research output: Contribution to journalArticlepeer-review

Abstract

Importance of the field: 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. Areas covered by this review: This review will discuss targeting of MEK which could lead to novel methods to control abnormal proliferation which arises in cancer and other proliferative diseases. This review will cover the scientific literature from 1980 to present and is a follow on from a review which focused on Emerging Raf Inhibitors published in this same review series. What the reader will gain: By reading this review the reader will understand the important roles that genetics play in the response of patients to MEK inhibitors, the potential of combining MEK inhibitors with other types of therapy, the prevention of cellular aging and the development of cancer stem cells. Take home message: 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 the suppression of cancer, proliferative diseases and aging.

Original languageEnglish
Pages (from-to)203-223
Number of pages21
JournalExpert Opinion on Emerging Drugs
Volume15
Issue number2
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Apoptosis
  • Cancer
  • ERK
  • Kinases
  • MEK
  • MEK inhibitors
  • Proliferative disorders
  • Protein phosphorylation
  • Signal transduction

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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