Advances in Targeting the Ras/Raf/MEK/Erk Mitogen-Activated Protein Kinase Cascade with MEK Inhibitors for Cancer Therapy

• Published in: Clinical cancer research 2008-01, Vol.14 (2), p.342-346
• Main Authors: FRIDAY, Bret B, ADJEI, Alex A
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Extracellular Signal-Regulated MAP Kinases - metabolism; Humans; map kinase; MAP Kinase Signaling System - drug effects; Medical sciences; Mitogen-Activated Protein Kinases - metabolism; Neoplasms - drug therapy; Neoplasms - enzymology; Pharmacology. Drug treatments; raf kinase; raf Kinases - metabolism; ras Proteins - metabolism; signal transduction; Small Molecule Libraries - pharmacology
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-4790

The identification of intracellular signaling cascades important for the growth and survival of cancer cells has led to the development of targeted cancer therapeutics aimed at blocking these signals. The mitogen-activated protein kinase (MAPK) pathway has a well-defined role in cancer biology and has been an important target in the development of targeted therapies. Recently, several small-molecule inhibitors of MAPK/extracellular signal–regulated kinase kinase (MEK), a key intermediary of MAPK signaling, have been developed and are currently being tested in clinical trials. Herein, we review the MAPK pathway, the development of small-molecule MEK inhibitors, and the results obtained to date with MEK inhibitors in human cancer trials.