Table 3 |
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Therapeutic strategies for targeting molecules/pathways involved in the pathogenesis of bone metastasis |
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Therapeutic strategy |
Target and rationale for therapy |
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Recombinant OPG construct |
Blocks RANKL and TRAIL pathway [69] |
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Soluble RANK-Fc |
Blocks the effect of RANKL without any effect on the TRAIL pathway [43-45] |
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Human monoclonal antibody to RANKL (denosumab) |
Blocks the effect of RANKL without any effect on the TRAIL pathway [72] |
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Oligonucleotides to NF-κB, P2X7 receptor antagonists |
Block the effect of NF-κB activation [97] |
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Humanized anti-PTHrP monoclonal antibody |
Inhibits PTHrP-mediated osteolysis via the RANKL pathway [41] |
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PDGFR antagonist (ST1571, Imatinib mesylate/Gleevec) |
Inhibits tumor growth and angiogenesis by inhibiting PDGFR tyrosine kinase signaling [98] |
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ETA receptor inhibitor (atrasentan) |
Blocks ET-1 mediated bone formation in prostate skeletal metastasis [55,58,59] |
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EMD121974 (cilengitide) |
Inhibits tumor-ECM interactions involved in tumor metastasis, growth, and angiogenesis [76] |
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MMP inhibitors |
Inhibit MMP mediated tumor growth, metastasis, and angiogenesis [99] |
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ECM, extracellular matrix; ET, endothelin; ETA, endothelin receptor subtype A; MMP, matrix metalloproteinase; NF-κB, nuclear factor-κB; OPG, osteoprotegerin; PDGF, platelet-derived growth factor; PTHrP, parathyroid hormone related peptide; RANKL, receptor activator of nuclear factor-κB ligand; TRAIL, TNF-related apoptosis-inducing ligand. |
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Virk and Lieberman Arthritis Research & Therapy 2007 9(Suppl 1):S5 doi:10.1186/ar2169 |
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