Prevention and Treatment of Bone Metastases

E.      J. Woodward; R.      E. Coleman

doi:10.2174/138161210793563581

Abstract

Certain primary tumours including breast and prostate cancers have a particular propensity for metastasis to bone. Metastatic bone disease can have significant impact on morbidity and mortality of cancer patients. Skeletal-morbidity (spinal cord compression, hypercalcaemia, fracture, need for radiotherapy and surgery to bone) can be effectively reduced by bisphosphonates, a class of antiresorptive drugs. They are also effective in relieving pain from bone metastases, and may improve survival in patients with accelerated bone resorption. Additionally, there is an exciting body of evidence that suggests these drugs may have anti-tumour effects that may be exploited to prevent or delay the development of bone metastases. Reported effects include inhibition of cancer cell migration, adhesion and invasion as well as anti-angiogenic and immunomodulating effects. The pre-clinical evidence is compelling, and some recently reported randomised clinical studies go part way to support their use in clinical practice at earlier stages of the disease to prevent bone metastases. However, further results are awaited before routine clinical use in the adjuvant setting can be recommended.

Keywords: Bone, metastasis, bisphosphonates, breast cancer, Bone Metastases, percalcaemia, resorptive drugs, Skeletal-morbidity, hy, anti-angiogenic, immunomodulating effects, cell migration, adhesion, invasion, bone-directed therapy, osteoblasts, osteoclasts, metastatic tumour growth, P-C-P backbone, non-nitrogen bisphosphonates, mevalonate pathway, isopentenyl diphosphate (IPP), dronate, pamidronate, Clo, Ibandronate, pa-midronate, testinal adverse effects, gastroin, Osteonecrosis, craniofacial radiotherapy, ovarian cancer lines, myeloma cells, prostate cancer, osteosarcoma, melanoma, lung can-cer, pancreatic cancer, letrozole, loss of Cenp-F, chromosome segregation, anti-angiogenic properties, tumour surveillance, UFT, Ewing's sarcoma, anti-tumour effect, prolonged survival, anti-tumour drugs, disease-free survival (DFS), Austrian Breast Cancer Study Group, (ABCSG), tamoxifen, anastrazole, endocrine-responsive breast cancer, bone-targeted therapy