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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We thank J. Fergus for technical assistance.
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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
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DOI: https://doi.org/10.1038/10533
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