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

Nat Med. 1999 Jul;5(7):810-6. doi: 10.1038/10533.

J S Sebolt-Leopold ¹, D T Dudley, R Herrera, K Van Becelaere, A Wiland, R C Gowan, H Tecle, S D Barrett, A Bridges, S Przybranowski, W R Leopold, A R Saltiel

Affiliations

Affiliation

1 Department of Cell Biology, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert, Ann Arbor, Michigan 48105, USA.

PMID: 10395327 DOI: 10.1038/10533

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.

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