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]

ETA 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; 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.

Virk and Lieberman Arthritis Research & Therapy 2007 9(Suppl 1):S5   doi:10.1186/ar2169