Antagonists of inhibitor of apoptosis (IAP) proteins are being developed as possible apoptosis-inducing cancer therapeutics. However, inhibition of IAPs can also stimulate osteoclasts through stabilization of the kinase NIK (which activates the alternative nuclear factor-κB (NF-κB) signalling pathway), indicating that IAP inhibition might increase bone metastasis. Yang et al. found that IAP antagonists can indeed enhance the growth of metastatic tumours in bone in vivo. They also determined that this could be reduced by co-treating mice with the bisphosphonate zoledronic acid, which inhibits osteoclasts.
ORIGINAL RESEARCH PAPER
Yang, C. et al. Anti-cancer IAP inhibition increases bone metastasis via unexpected osteoclast activation. Cancer Discov. 26 Dec 2012 (doi:10.1158/2159-8290.CD-12-0271)
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Balancing risks and benefits. Nat Rev Cancer 13, 81 (2013). https://doi.org/10.1038/nrc3465
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DOI: https://doi.org/10.1038/nrc3465