Tumor metastasis to bone

Table 3 Therapeutic strategies for targeting molecules/pathways involved in the pathogenesis of bone metastasis

Therapeutic strategy	Target and rationale for therapy
Recombinant OPG construct	Blocks RANKL and TRAIL pathway [69]
Soluble RANK-Fc	Blocks the effect of RANKL without any effect on the TRAIL pathway [43-45]
Human monoclonal antibody to RANKL (denosumab)	Blocks the effect of RANKL without any effect on the TRAIL pathway [72]
Oligonucleotides to NF-κB, P2X7 receptor antagonists	Block the effect of NF-κB activation [97]
Humanized anti-PTHrP monoclonal antibody	Inhibits PTHrP-mediated osteolysis via the RANKL pathway [41]
PDGFR antagonist (ST1571, Imatinib mesylate/Gleevec)	Inhibits tumor growth and angiogenesis by inhibiting PDGFR tyrosine kinase signaling [98]
ET_A receptor inhibitor (atrasentan)	Blocks ET-1 mediated bone formation in prostate skeletal metastasis [55,58,59]
EMD121974 (cilengitide)	Inhibits tumor-ECM interactions involved in tumor metastasis, growth, and angiogenesis [76]
MMP inhibitors	Inhibit MMP mediated tumor growth, metastasis, and angiogenesis [99]

ECM, extracellular matrix; ET, endothelin; ET_A, 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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