» Articles » PMID: 17346150

Signaling Through RAS-RAF-MEK-ERK: from Basics to Bedside

Overview
Journal Curr Med Chem
Specialty Chemistry
Date 2007 Mar 10
PMID 17346150
Citations 49
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Frequency of and mutations in colorectal carcinoma and their association with clinical-pathological characteristics in a tertiary hospital in Kenya.

Gakinya S, Njau A, Abdallah A, Nzioka A, Ogutu J Front Med (Lausanne). 2024; 11:1433120.

PMID: 39364024 PMC: 11446768. DOI: 10.3389/fmed.2024.1433120.


MEK/ERK and PI3K/AKT pathway inhibitors affect the transformation of myelodysplastic syndrome into acute myeloid leukemia via H3K27me3 methylases and de‑methylases.

Zheng Z, Chen X, Zhang Y, Ren F, Ma Y Int J Oncol. 2023; 63(6).

PMID: 37921060 PMC: 10631768. DOI: 10.3892/ijo.2023.5588.


The Mutational Landscape of Myeloid Leukaemia in Down Syndrome.

de Castro C, Cadefau M, Cuartero S Cancers (Basel). 2021; 13(16).

PMID: 34439298 PMC: 8394284. DOI: 10.3390/cancers13164144.


The Importance of Being PI3K in the RAS Signaling Network.

Cuesta C, Arevalo-Alameda C, Castellano E Genes (Basel). 2021; 12(7).

PMID: 34356110 PMC: 8303222. DOI: 10.3390/genes12071094.


Development of a myelodysplastic/myeloproliferative neoplasm-unclassifiable in a patient with acute myeloid leukemia: a case report and literature review.

Zhao M, Sun J, Liu S, Fan H, Fu Y, Tan Y J Int Med Res. 2021; 49(5):3000605211018426.

PMID: 34057843 PMC: 8753788. DOI: 10.1177/03000605211018426.