Signaling Through RAS-RAF-MEK-ERK: from Basics to Bedside
Overview
Authors
Affiliations
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.
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.
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.
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.