Review

From basic research to clinical development of MEK1/2 inhibitors for cancer therapy

Christophe Frémin and Sylvain Meloche^*

• * Corresponding author: Sylvain Meloche sylvain.meloche@umontreal.ca

Author Affiliations

Institut de Recherche en Immunologie et Cancérologie and Departments of Pharmacology and Molecular Biology, Université de Montréal, Montreal, Quebec H3C 3J7, Canada

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Journal of Hematology & Oncology 2010, 3:8 doi:10.1186/1756-8722-3-8

Published: 11 February 2010

Abstract

The Ras-dependent Raf/MEK/ERK1/2 mitogen-activated protein (MAP) kinase signaling pathway is a major regulator of cell proliferation and survival. Not surprisingly, hyperactivation of this pathway is frequently observed in human malignancies as a result of aberrant activation of receptor tyrosine kinases or gain-of-function mutations in RAS or RAF genes. Components of the ERK1/2 pathway are therefore viewed as attractive candidates for the development of targeted therapies of cancer. In this article, we briefly review the basic research that has laid the groundwork for the clinical development of small molecules inhibitors of the ERK1/2 pathway. We then present the current state of clinical evaluation of MEK1/2 inhibitors in cancer and discuss challenges ahead.