Bisphosphonate actions on bone and visceral metastases.

Abstract

Bone abundantly stores a variety of growth factors and thus provides migrating cancer cells with fertile soil. Osteoclastic bone resorption releases these growth factors providing fertile environment, which allows colonizing cancer cells to proliferate and survive. Consequently, cancer cells produce a variety of factors that in turn influence bone metabolism. This intimate partnership between cancer cells and bone will be a driving force to develop and progress bone metastases. Accordingly, suppression of osteoclastic bone resorption should be a logic approach to inhibit bone metastases. Bisphosphonates (BPs), specific inhibitors of osteoclasts, have been widely used for the treatment of bone metastases in cancer patients. In addition, recent studies suggest the possibility that BPs can reduce visceral metastases by inhibiting cell growth and inducing apoptosis in cancer cells. In this chapter, the authors will review the recent experimental results regarding the effects of BPs on bone and visceral metastases and also show their own data obtained using animal models of breast cancer metastasis. Accumulating data suggest that there is no doubt that BPs are beneficial for the treatment of existing bone metastases, while the beneficial effects of BPs on visceral metastases are not warranted yet.