Targeting the vicious cycle of cancer-induced bone disease with TRAIL and bisphosphonates

Funded Activity Summary

The most serious clinical problem with patients with many forms of solid tumours is metastasis to bone, which leads to potentially debilitating complications that can cause erosion of the patient's quality of life, and eventually death. Unfortunately, bony metastases usually occur before pre-emptive treatments can be applied to prevent it. We have recently shown that recombinant soluble TRAIL is a potent anticancer agent that prevents cancer-induced bone destruction in a mouse model by directly targeting cancer cells within bone, and with no evidence of toxic side effects to normal tissues. Death receptor targeting by TRAIL, and bisphosphonates induce cancer cell apoptosis through different but overlapping signaling pathways. Therefore, combination of the two approaches may facilitate killing of tumour cells that resist death induction through either one of the pathways. Combination therapy may also reduce the probability of acquired resistance to either therapy. We propose that a combinatorial approach, using bisphosphonates to selectively target osteoclasts and TRAIL to selectively target cancer cells, would be an ideal therapeutic and safe approach to delay, slow or completely eliminate growth of cancer within bone.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $443,696.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Orthopaedics

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

TRAIL | bisphosphonates | bone cancer | breast cancer | multiple myeloma | osteolysis | osteosarcoma

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