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

Citation
Js. Sebolt-leopold et al., Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo, NAT MED, 5(7), 1999, pp. 810-816
Citations number
37
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Journal title
NATURE MEDICINE
ISSN journal
10788956 → ACNP
Volume
5
Issue
7
Year of publication
1999
Pages
810 - 816
Database
ISI
SICI code
1078-8956(199907)5:7<810:BOTMKP>2.0.ZU;2-X
Abstract
The mitogen-activated protein kinase pathway is thought to be essential in cellular growth and differentiation. Here we report the discovery of a high ly 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 carci nomas of both mouse and human origin after treatment with this inhibitor. E fficacy was achieved with a wide range of doses with no signs of toxicity, and correlated with a reduction in the levels of activated mitogen-activate d protein kinase in excised tumors. These data indicate that MEK inhibitors represent a promising, noncytotoxic approach to the clinical management of colon cancer.