New role for an established drug? Bisphosphonates as potential anticancer agents.

As a result of their ability to effectively reduce the risk of skeletal-related events, bisphosphonates (BPs) were incorporated into clinical practice over a decade ago, leading to a new treatment paradigm for patients with skeletal involvement from advanced cancer. BPs are now a well-established treatment option in this setting. Our review of the literature found that in addition to maintaining bone health in patients with malignant bone lesions and patients at risk for cancer therapy-induced bone loss, emerging preclinical and clinical data suggest that BPs may also have anticancer activity. Later generation, nitrogen-containing BPs (N-BPs), such as zoledronic acid (ZOL), inhibit the mevalonate pathway, subsequently inhibiting a number of cellular functions in bone-resorbing osteoclasts. In addition, N-BPs inhibit cancer cell proliferation, viability, motility, invasion and angiogenesis; induce cancer cell apoptosis; and act in synergy with antineoplastic agents. N-BPs, especially ZOL, may be useful as anticancer agents. As evidence continues to emerge, another shift in cancer treatment paradigms, in which N-BPs are considered for their anticancer activity as well as palliative effects, may be approaching.