Blockade of the map kinase pathway suppresses growth of colon tumors in vivo

ABSTRACT The mitogen-activated protein kinase pathway is thought to be essential in cellular growth and differentiation. Here we report the discovery of a highly potent and selective

inhibitor of the upstream kinase MEK that is orally active. Tumor growth was inhibited as much as 80% in mice with colon carcinomas of both mouse and human origin after treatment with this

inhibitor. Efficacy was achieved with a wide range of doses with no signs of toxicity, and correlated with a reduction in the levels of activated mitogen-activated protein kinase in excised

tumors. These data indicate that MEK inhibitors represent a promising, noncytotoxic approach to the clinical management of colon cancer. Access through your institution Buy or subscribe This

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ACKNOWLEDGEMENTS We thank J. Fergus for technical assistance. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Cell Biology, Division of Warner-Lambert, Parke-Davis Pharmaceutical

Research, 2800 Plymouth Road, Ann Arbor, 48105, Michigan, USA Judith S. Sebolt-Leopold, David T. Dudley, Roman Herrera, Keri Van Becelaere, Amy Wiland, Richard C. Gowan & Alan R.

Saltiel * Department of Chemistry, Division of Warner-Lambert, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor, 48105, Michigan, USA Haile Tecle, Stephen D. Barrett & 

Alexander Bridges * Department of Cancer Research, Division of Warner-Lambert, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor, 48105, Michigan, USA Sally Przybranowski 

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permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sebolt-Leopold, J., Dudley, D., Herrera, R. _et al._ Blockade of the MAP kinase pathway suppresses growth of colon tumors _ in vivo_. _Nat

Med_ 5, 810–816 (1999). https://doi.org/10.1038/10533 Download citation * Received: 31 March 1999 * Accepted: 30 April 1999 * Issue Date: July 1999 * DOI: https://doi.org/10.1038/10533 SHARE

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