| First Author | Lalaoui N | Year | 2016 |
| Journal | Cancer Cell | Volume | 29 |
| Issue | 2 | Pages | 145-58 |
| PubMed ID | 26859455 | Mgi Jnum | J:231452 |
| Mgi Id | MGI:5771593 | Doi | 10.1016/j.ccell.2016.01.006 |
| Citation | Lalaoui N, et al. (2016) Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics. Cancer Cell 29(2):145-58 |
| abstractText | Birinapant is a smac-mimetic (SM) in clinical trials for treating cancer. SM antagonize inhibitor of apoptosis (IAP) proteins and simultaneously induce tumor necrosis factor (TNF) secretion to render cancers sensitive to TNF-induced killing. To enhance SM efficacy, we screened kinase inhibitors for their ability to increase TNF production of SM-treated cells. We showed that p38 inhibitors increased TNF induced by SM. Unexpectedly, even though p38 is required for Toll-like receptors to induce TNF, loss of p38 or its downstream kinase MK2 increased induction of TNF by SM. Hence, we show that the p38/MK2 axis can inhibit or promote TNF production, depending on the stimulus. Importantly, clinical p38 inhibitors overcame resistance of primary acute myeloid leukemia to birinapant. |
