Bisphosphonates and cancer-induced bone disease: beyond their antiresorptive activity

Bisphosphonates are primarily known for their ability to inhibit osteoclast-mediated bone resorption. They are an indispensable part of therapy for patients with cancers that cause osteolysis. However, there is now a growing body of evidence from preclinical research showing that bisphosphonates also exhibit antitumor activity, both in vitro and in vivo. They can affect molecular mechanisms of tumor cell adhesion, invasion, and proliferation; reinforce the effects of cytotoxic agents in a synergistic manner; and exhibit antiangiogenic and immunomodulatory effects. These preclinical findings reveal exciting ways of optimizing bisphosphonate therapy in oncology to fully exploit their antitumor potential.