Unraveling the complexities of the Raf/MAP kinase pathway for pharmacological intervention.
The Ras-MAP kinase pathway has attracted much attention from academic and pharmaceutical laboratories because of its central role in regulating tumor cell growth and survival, differentiation and angiogenesis. Although the central players in this pathway -Ras, Raf, and MEK - have been well studied, how best to exploit them for therapeutic gain has eluded oncology researchers in the past. Several small-molecule inhibitors that target specific steps of the MAP kinase cascade have recently entered the clinical arena. While we await answers on their ultimate therapeutic use, the availability of translational assays for monitoring target suppression will no doubt play a significant role in optimizing our chances of success.
Herrera
Roman
R
Department of Cancer Molecular Sciences, Pfizer Global Research & Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.
Sebolt-Leopold
Judith S
JS
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009369:Neoplasms / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human