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Targeting mitogen-activated protein kinase kinase (MEK) in solid tumors

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Abstract

The Raf-mitogen activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) protein kinase signaling cascade is an important intracellular pathway whose activation influences many fundamental cellular processes and whose aberrancy is associated with cancer cell growth. In addition to activation from within by, for example, Raf mutations, this pathway is frequently activated from above by mutated Ras or epidermal growth factor receptor (EGFR). Given the near ubiquity of derangements affecting at least part of this network in cancer, there is a strong and clear rationale for interrupting it. In recent times, in colorectal and lung cancer, Ras and EGFR mutant status have been shown to be critically important and mutually exclusive predictors of response to anti-EGFR therapies. These developments underline the importance of targeting downstream effectors, and MEK inhibition has been the subject of intense scientific and clinical research for some time now. This article reviews the current status of MEK inhibitors with regard to their clinical development.

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Acknowledgements

The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Conflict of interest statement

No funds were received in support of this study and no benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript.

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  1. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, 10/13N240G, Bethesda, MD, 20892, USA

    Austin Duffy & Shivaani Kummar

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  1. Austin Duffy
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Correspondence to Austin Duffy.

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Duffy, A., Kummar, S. Targeting mitogen-activated protein kinase kinase (MEK) in solid tumors. Targ Oncol 4, 267–273 (2009). https://doi.org/10.1007/s11523-009-0125-x

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