Increased resistance to proteasome inhibitors in multiple myeloma mediated by cIAP2--implications for a combinatorial treatment.

ABSTRACT: Despite the introduction of new treatment options for multiple myeloma (MM), a majority of patients relapse due to the development of resistance. Unraveling new mechanisms underlying resistance could lead to identification of possible targets for combinatorial treatment. Using TRAF3 deleted/mutated MM cell lines, we evaluated the role of the cellular inhibitor of apoptosis 2 (cIAP2) in drug resistance and uncovered the plausible mechanisms underlying this resistance and possible strategies to overcome this by combinatorial treatment. In MM, cIAP2 is part of the gene signature of aberrant NF-κB signaling and is heterogeneously expressed amongst MM patients. In cIAP2 overexpressing cells a decreased sensitivity to the proteasome inhibitors bortezomib, MG132 and carfilzomib was observed. Gene

SUBMITTER: Fristedt Duvefelt C 

PROVIDER: S-EPMC4653030 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature