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lüll From basic research to clinical development of MEK1/2 inhibitors for cancer therapy Fremin C; Meloche SJ Hematol Oncol 2010[Feb]; 3 (ä): 8The 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.|*Research/trends[MESH]|Animals[MESH]|Antineoplastic Agents/therapeutic use[MESH]|Clinical Trials as Topic/*methods/trends[MESH]|Humans[MESH]|MAP Kinase Kinase 1/*antagonists & inhibitors[MESH]|MAP Kinase Kinase 2/*antagonists & inhibitors[MESH]|Models, Biological[MESH]|Neoplasms/*drug therapy[MESH]|Protein Kinase Inhibitors/*therapeutic use[MESH]|Research Design[MESH] |