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Preclinical evidence for the effect of bisphosphonates and cytotoxic drugs on tumor cell invasion

Woodward, Julia K. L.a; Coleman, Robert E.a; Holen, Ingunna

Review Paper

Bisphosphonates (BPs) are stable pyrophosphate analogs currently used in the treatment of patients with metastatic bone disease, known to affect bone resorption by reducing osteoclast activity. Use of these drugs in adjuvant therapy is currently under investigation following reports of an effect of BPs on tumor cell apoptosis in preclinical models. Recent evidence has suggested that BPs might also affect tumor cell invasion in vitro, and the component processes of adhesion, migration and degradation, through mechanisms including inhibition of prenylation of intracellular small GTPases such as Ras and Rho. The effects potentially may be enhanced through co-administration with chemotherapy agents, as both synergistic and additive effects have been described in vitro. This review discusses the preclinical evidence for the potential use of BPs and cytotoxic drugs for inhibiting tumor cell invasion, a key process in cancer progression.

aAcademic Unit of Clinical Oncology, Division of Genomic Medicine, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK

Correspondence to J. K. L. Woodward, Clinical Oncology, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK

Tel: +44 114 271 2375; fax: +44 114 271 1711;

e-mail: j.k.woodward@sheffield.ac.uk

Received 19 July 2004 Revised form accepted 18 August 2004

© 2005 Lippincott Williams & Wilkins, Inc.