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Signaling through RAS-RAF-MEK-ERK: from basics to bedside.
- Source :
-
Current medicinal chemistry [Curr Med Chem] 2007; Vol. 14 (5), pp. 601-23. - Publication Year :
- 2007
-
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.
- Subjects :
- Animals
Cytoplasm enzymology
Cytoplasm genetics
Extracellular Signal-Regulated MAP Kinases genetics
GTP-Binding Proteins physiology
Genes, ras genetics
Humans
Intracellular Signaling Peptides and Proteins physiology
MAP Kinase Kinase Kinases genetics
Signal Transduction genetics
raf Kinases genetics
Extracellular Signal-Regulated MAP Kinases physiology
Genes, ras physiology
MAP Kinase Kinase Kinases physiology
Signal Transduction physiology
raf Kinases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0929-8673
- Volume :
- 14
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Current medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17346150
- Full Text :
- https://doi.org/10.2174/092986707780059670