Antitumor effects of bisphosphonates: from the laboratory to the clinic

The use of bisphosphonates has focused on their antibone resorptive effects but recent studies have shown that these drugs also possess a variety of antitumor effects in the laboratory that are now being observed in clinical trials.

It is becoming increasingly clear that bisphosphonates - especially the more potent nitrogen-containing bisphosphonates (N-BPs) and, in particular, zoledronic acid - show a multitude of antitumor effects in the laboratory. These drugs have been shown to induce apoptosis in a variety of cancer cells and enhance the antitumor effects of a variety of treatments including steroids, chemotherapeutic agents and hormonal therapies as well as many classes of new anticancer drugs. In addition, the agents inhibit vasculogenesis and angiogenesis. The N-BPs also show immunostimulatory effects that have been shown to have potent antitumor effects. They also block tumor cell adhesion making tumor cells more susceptible to the cytotoxic effects of chemotherapy as well as migration and invasion of tumor cells. Recent clinical trials have demonstrated their ability to not only reduce skeletal morbidity but also delay time to progression of the malignant disease in some but not all studies and improve overall survival in other trials.

Emerging laboratory and clinical data now support the important antitumor effects of N-BPs in both solid and hematological cancers. It will be important to determine whether the combination of these drugs with other agents with not only chemotherapy but newer agents may enhance these effects.