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Targeting Aberrant RAS/RAF/MEK/ERK Signaling for Cancer Therapy

by Ufuk Degirmenci 1, Mei Wang 2,* and Jiancheng Hu 1,2,*
1
Division of Cellular and Molecular Research, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore 169610, Singapore
2
Cancer and Stem Cell Biology Program, Duke-NUS Medical School, 8 College Road, Singapore 169857, Singapore
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(1), 198; https://doi.org/10.3390/cells9010198 (registering DOI)
Received: 12 December 2019 / Revised: 29 December 2019 / Accepted: 10 January 2020 / Published: 13 January 2020
(This article belongs to the Special Issue GTPase Pathways in Health and Diseases)
The RAS/RAF/MEK/ERK (MAPK) signaling cascade is essential for cell inter- and intra-cellular communication, which regulates fundamental cell functions such as growth, survival, and differentiation. The MAPK pathway also integrates signals from complex intracellular networks in performing cellular functions. Despite the initial discovery of the core elements of the MAPK pathways nearly four decades ago, additional findings continue to make a thorough understanding of the molecular mechanisms involved in the regulation of this pathway challenging. Considerable effort has been focused on the regulation of RAF, especially after the discovery of drug resistance and paradoxical activation upon inhibitor binding to the kinase. RAF activity is regulated by phosphorylation and conformation-dependent regulation, including auto-inhibition and dimerization. In this review, we summarize the recent major findings in the study of the RAS/RAF/MEK/ERK signaling cascade, particularly with respect to the impact on clinical cancer therapy. View Full-Text
Keywords: RAS GTPases; RAF family kinases; Ras/RAF/MEK/ERK signaling; BRAF(V600E); RAF inhibitors; paradoxical activation; protein–protein interactions; synthetic lethal; neoplasm RAS GTPases; RAF family kinases; Ras/RAF/MEK/ERK signaling; BRAF(V600E); RAF inhibitors; paradoxical activation; protein–protein interactions; synthetic lethal; neoplasm
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Degirmenci, U.; Wang, M.; Hu, J. Targeting Aberrant RAS/RAF/MEK/ERK Signaling for Cancer Therapy. Cells 2020, 9, 198.

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