Signaling through RAS-RAF-MEK-ERK: from basics to bedside.

Abstract:

:Aberrant signaling caused by mutations in the RAS-RAF-MEK-ERK pathway and its upstream activators critically contributes to human tumor development. Strategies, which aim at inhibiting hyperactive signaling molecules, appear conceptually straight forward, but their translation into clinical practice has been hampered by many setbacks. Understanding structure, function and regulation of this intracellular pathway as well as its crosstalk with other signaling activities in the cell will be essential to ensure reasonable usage of new therapeutic possibilities. This review provides an understanding of this signaling cascade as revealed by genetic and biochemical approaches and discusses the existing or arising possibilities to interfere with unphysiological activation in cancer. Signaling aberrations and signal transduction therapies will be discussed exemplary for two types of hematological neoplasia, acute myeloid leukemia (AML) and the myelodysplastic syndromes (MDS). In the future understanding the role of tumor stem cells, both as a source of tumor recurrence and tumor heterogeneity, the signals controlling their fate as well as epigenetic changes in cancer will be the next critical steps to further advance the applicability of these novel therapeutic strategies.

journal_name

Curr Med Chem

authors

Zebisch A,Czernilofsky AP,Keri G,Smigelskaite J,Sill H,Troppmair J

doi

10.2174/092986707780059670

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

601-23

issue

5

eissn

0929-8673

issn

1875-533X

journal_volume

14

pub_type

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