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Annals of Oncology 14:1468-1476, 2003
© 2003 European Society for Medical Oncology

The antineoplastic role of bisphosphonates: from basic research to clinical evidence

D. Santini1,+, U. Vespasiani Gentilucci2, B. Vincenzi1, A. Picardi2, F. Vasaturo3, A. La Cesa1, N. Onori4, S. Scarpa3 and G. Tonini1

Interdisciplinary Center for Biomedical Research (CIR), 1 Oncology, 2 Laboratory of Internal Medicine and Hepathology and 4 Clinical Pharmacology, University Campus Bio-Medico, Rome; 3 Department of Experimental Medicine and Pathology, ‘La Sapienza’ University, Rome, Italy

Received 19 December 2002; revised 7 March 2003; accepted 14 April 2003

Abstract

Bisphosphonates are now well established as successful agents for the prevention and treatment of postmenopausal osteoporosis, corticosteroid-induced bone loss and Paget’s disease. Bisphosphonates have also recently become important in the management of cancer-induced bone disease, and they now have a widely recognized role for patients with multiple myeloma and bone metastases secondary to breast cancer and prostate cancer. Recent studies suggest that, besides the strong antiosteoclastic activity, the efficacy of such compounds in the oncological setting could also be due also to direct antitumor effect, exerted at different levels. Here, after a brief analysis of the chemical structure, we will review the antineoplastic and biological properties of bisphosphonates. We will start from well estabilished mechanisms of action and go on to discuss the latest evidence and hypotheses. In particular, we will review the antiresorptive properties in malignant osteolysis and the recent evidence of a direct antitumor effect. Furthermore, this review will analyze the influence of bisphosphonates on cancer growth factor release, their effect on cancer cell adhesion, invasion and viability, the proapoptotic potential on cancer cells, the antiangiogenic effect, and, finally, the immunomodulating properties of bisphosphonates on the {gamma}{delta} T cell population.

Key words: angiogenesis, antineoplastic, apoptosis, bisphosphonates, clinical and preclinical evidence


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