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01.12.2014 | Leading Article

The Biology and Clinical Development of MEK Inhibitors for Cancer

verfasst von: Jason J. Luke, Patrick A. Ott, Geoffrey I. Shapiro

Erschienen in: Drugs | Ausgabe 18/2014

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Abstract

The mitogen-activated protein kinase kinases (MAPKK) MEK1 and MEK2 are integral members of the MAPK/ERK signaling pathway and are of interest in the development of anti-cancer therapeutics. The MAPK/ERK pathway is dysregulated in more than 30 % of cancers, predominately by mutations in RAS and BRAF proteins, and MEK serves as a potential downstream target for both of these. The biology of MEK inhibition is complex, as the molecule is differentially regulated by upstream RAS or RAF. This has impacted on the past development of MEK inhibitors as treatments for cancer and may be exploited in more rational, molecularly selected drug development plans in the future. The role of MEK in cancer and the mechanism of action of MEK inhibitors is reviewed. Furthermore, MEK inhibitors that are available in standard practice, as well as those most advanced in clinical development, are discussed. Finally, next steps in the development of MEK inhibitors are considered.

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Titel: The Biology and Clinical Development of MEK Inhibitors for Cancer
verfasst von: Jason J. Luke
Patrick A. Ott
Geoffrey I. Shapiro
Publikationsdatum: 01.12.2014
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 18/2014
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-014-0315-4

Springer Medizin

Abstract

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