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

2008; American Association for Cancer Research; Volume: 14; Issue: 2 Linguagem: Inglês

10.1158/1078-0432.ccr-07-4790

1557-3265

Bret B. Friday, Alex A. Adjei,

PI3K/AKT/mTOR signaling in cancer

Abstract 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.