title: The anti-tumour effects of zoledronic acid.
abstract: Bone is the most common site for metastasis in patients with solid tumours. Bisphosphonates are an effective treatment for preventing skeletal related events and preserving quality of life in these patients. Zoledronic acid (ZA) is the most potent osteoclast inhibitor and is licensed for the treatment of bone metastases. Clodronate and pamidronate are also licensed for this indication. In addition, ZA has been demonstrated to exhibit antitumour effect. Direct and indirect mechanisms of anti-tumour effect have been postulated and at many times proven. Evidence exists that ZA antitumour effect is mediated through inhibition of tumour cells proliferation, induction of apoptosis, synergistic/additive to inhibitory effect of cytotoxic agents, inhibition of angiogenesis, decrease tumour cells adhesion to bone, decrease tumour cells invasion and migration, disorganization of cell cytoskeleton and activation of specific cellular antitumour immune response. There is also clinical evidence from clinical trials that ZA improved long term survival outcome in cancer patients with and without bone metastases. In this review we highlight the preclinical and clinical studies investigating the antitumour effect of bisphosphonates with particular reference to ZA.
authors.affiliation: AlFaisal University College of Medicine, PO Box 50927, Riyadh 11533, Saudi Arabia; King Faisal Specilalist Hospital and Research Center, MBC J64, PO Box 40047, Jeddah 21499, Saudi Arabia.
authors.forename: Jamal
authors.initials: J
authors.lastname: Zekri
authors.affiliation: Jeddah Cancer Centre, Dr. Erfan & Bagedo General Hospital, King Fahd Street, PO Box 6519, Jeddah 21452, Saudi Arabia.
authors.forename: Maged
authors.initials: M
authors.lastname: Mansour
authors.affiliation: AlFaisal University College of Medicine, PO Box 50927, Riyadh 11533, Saudi Arabia; King Faisal Specilalist Hospital and Research Center, MBC J64, PO Box 40047, Jeddah 21499, Saudi Arabia.
authors.forename: Syed Mustafa
authors.initials: SM
authors.lastname: Karim
keywords: Angiogenesis; Antitumour; Apoptosis; Bisphosphonates; T-cells; Zoledronic acid