Research ArticleSepsis

ALK is a therapeutic target for lethal sepsis

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Science Translational Medicine  18 Oct 2017:
Vol. 9, Issue 412, eaan5689
DOI: 10.1126/scitranslmed.aan5689

Taking the STING out of sepsis

Despite the existence of antibiotic therapy, sepsis is associated with a high mortality rate. Zeng et al. screened a library of kinase inhibitors to identify drugs that targeted the STING (stimulator of interferon genes) pathway, which was up-regulated in mononuclear cells from patients with sepsis. The authors found that STING is activated by anaplastic lymphoma kinase (ALK), which interacts with epidermal growth factor receptor and signals through downstream serine-threonine protein kinase AKT. Inhibiting ALK-STING signaling genetically or with oral drug treatment improved survival in mouse models of sepsis and endotoxemia. The ALK-STING pathway could be a useful target for drug development for sepsis.