Anti-Tumor Effect of Bisphosphonates: a New Therapeutic Perspective

Abstract

Bisphosphonates are potent osteoclast-mediated bone reabsorption inhibitors. These drugs are effective in reducing serum calcium levels in patients with malignant hypercalcaemia, as well as in bone pain, osteoporosis and bone metastasis treatment. Several studies have demonstrated that bisphosphonates are effective in other cell types than osteoclasts. In tumour cells they can act inducing apoptosis, inhibiting cell proliferation, inhibiting cell adhesion and invasion or bone metastasis. The underlying molecular mechanism to these effects seems to be the inhibition of mevalonate pathway enzymes, which leads to a prenilation impairment of GTPases like Ras and Rho, important in maintaining cellular cytoskeleton integrity and vesicles trafficking. Evidences from recent laboratorial and clinical studies suggest that bisphosphonates have an important role as a supplemental, and possibly as complementary treatment in cancer therapy. A more complete understanding concerning the anti-tumor effect of these drugs may suggest new and selective therapeutical possibilities.