Emma P. Shumeyko
Jun 1, 2016
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Journal
Clinical Pharmacology & Therapeutics
Abstract
Birinapant, an smac-mimetic (SM), is currently being studied in clinical trials as a drug to treat cancer. SM targets diseases that are sensitive to tumor necrosis factor (TNF)-induced killing by inhibiting apoptosis proteins and inducing TNF secretion. Lalaoui et al. aimed to enhance SM efficacy by examining the ability of p38 kinase inhibitors to increase TNF production of SMtreated cells. The authors show that, depending on the stimulus used, TNF production can be inhibited or stimulated by the p38/MK2 axis and the combination of SM and p38 inhibitors was well tolerated in vivo. This has important clinical implications since p38 inhibitors overcome birinapant resistance in primary acute myeloid leukemia. Lalaoui et al. Cancer Cell 29, 145–158 (2016). Treating Autoimmunity Through Antigen-Specific Regulatory Networks