Targeting multidrug resistance protein 1 (mdr1) potentiates smac-mimetic therapy to kill leukemic stem cells and overcome resistance in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive disease with a current 5-year survival rate of only ∼25%, therefore development of effective treatments towards resistant AML is urgently needed. Potential mechanisms of therapy resistance include overexpression of members of the inhibitor of apoptosis protein (IAP) family. Natural IAP antagonists such as second-mitochondria-derived activator of ca spases (Smac) exist, leading to the pharmaceutical development of Smac-mimetics (SMs). The clinical SM birinapant has been trialed in AML and solid cancers, as well as in hepatitis B virus (HBV), with variable and limited success.

Source: Experimental Hematology - July 31, 2019 Category: Hematology Authors: Emma Morrish, Anthony Copeland, Natasha Silke, Jessica Beach, Elizabeth Christie, Jarrod Sandow, Gregor Ebert, Liana Mackiewicz, Kate Jarman, Donia Moujalled, Giovanna Pomilio, Karla Fischer, Mark Dawson, David Bowtell, Marc Pellegrini, Andrew Webb, Andre Tags: 3100 Source Type: research