Bisphosphonates inhibit osteoclast-mediated
bone resorption, which is increased when
cancer cells invade bone, and are used in the treatment of metastatic
bone disease to reduce the risk of skeletal-related events. In addition, preclinical studies have shown that
bisphosphonates, especially potent
nitrogen-containing
bisphosphonates, have direct anticancer actions. Anticancer activity includes induction of apoptosis, and inhibition of invasion, in addition to synergistic activity with
chemotherapy agents, antiangiogenic properties, and modulating effects on the immune system. In terms of potential clinical anticancer activity, early data suggest that
zoledronic acid may have a role to play in preventing metastatic disease. The definitive answer is not known as yet; however, with more than 20,000 patients with breast, prostate, or
lung cancer currently participating in adjuvant
bisphosphonate randomized trials, results should be available in the next few years. This will establish whether
bisphosphonates given early in the course of
cancer will be able to prevent formation of
metastases, in or out of the bone environment. This review will focus on emerging evidence of the anticancer activities of
bisphosphonates and possible underlying mechanisms of action.