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

JS Sebolt-Leopold, DT Dudley, R Herrera… - Nature medicine, 1999 - nature.com
JS Sebolt-Leopold, DT Dudley, R Herrera, KV Becelaere, A Wiland, RC Gowan, H Tecle…
Nature medicine, 1999nature.com
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 …
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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