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

      Nature medicine

      Animals, Benzamides, pharmacology, therapeutic use, Cadherins, analysis, Calcium-Calmodulin-Dependent Protein Kinases, antagonists & inhibitors, Cell Cycle, drug effects, Cell Division, Colonic Neoplasms, drug therapy, enzymology, pathology, physiopathology, Enzyme Activation, Enzyme Inhibitors, Female, Hepatocyte Growth Factor, Humans, Male, Mice, Mice, Inbred Strains, Mice, Nude, Neoplasm Invasiveness, prevention & control, Signal Transduction, Transplantation, Heterologous, Tumor Cells, Cultured

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          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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          Journal
          10395327
          10.1038/10533

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