BoneKEy Reports | BoneKEy Watch
NF-κB inhibitor could be a novel treatment for multiple myeloma
DOI:10.1038/bonekey.2012.218
New therapeutic opportunities are desperately needed for multiple myeloma (MM), particularly in relation to the tendency for patients to exhibit drug resistance to bortezomib. Fabre et al. investigated the potential of PBS-1086, a potent inhibitor of NF-κB, a transcription factor known to promote osteolytic bone lesions in MM.
No NF-κB inhibitor has yet gone beyond pre-clinical development, but PBS-1086 displays some attractive characteristics. It was shown here to inhibit the canonical and noncanonical pathways through which NF-κB activity is achieved. PBS-1086 was also potently cytotoxic but selective, as it promoted apoptosis specifically in MM cells in vitro. It was also active in the microenvironment within bone, resisting the antiapoptotic and proliferative signals from bone marrow stem cells.
In vivo studies demonstrated that PBS-1086 was able to suppress tumor growth in a mouse xenograft model of human MM, where it was associated with a reduction in MM activity and a higher overall survival rate. However, probably the most interesting finding was that PBS-1086 overcomes resistance to bortezomib in vitro, suggesting that it could be developed as a synergistic co-therapy.
Editor’s comment: This preclinical study opens new avenues for the treatment of MM with bone lesions using a dual inhibitor of the canonical and noncanonical NF-κB pathways.
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