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© 2019 Zennadi R. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

SHORT REVIEW | OPEN ACCESSDOI: 10.23937/2469-5696/1410038

MEK1/2 as a Therapeutic Target in Sickle Cell Disease

Rahima Zennadi*

Division of Hematology and Duke Comprehensive Sickle Cell Center, Department of Medicine, Duke University Medical Center, North Carolina, USA


Identification of novel therapeutic targets has improved diagnostics and treatment of many diseases. Many innovative treatment strategies have been developed based on the newly identified biomarkers and key molecules. Most of the research focused on ways to manipulate signaling pathways by activating or suppressing them, validate new therapeutic targets for treatment, and epigenetic treatment of diseases. With the identification of aberrations in multiple growth pathways, the focus then shifted to the small molecules involved in these pathways for targeted therapy. In this communication/short review, we highlight the importance of identification of abnormal activation of the mitogen-activated protein kinase (MAPK), ERK1/2, and its upstream mediator MEK1/2, in erythrocytes in patients with sickle cell disease (SCD) critical for the adhesive interactions of these cells with the endothelium, and leukocytes promoting circulatory obstruction leading to tissue ischemia and infraction. We also discuss how targeting this signaling cascade with MEK1/2 inhibitors can reverse acute vasoocclusive crises in SCD.