Molecular and preclinical models enhancing anti-tumour activity of zoledronic acid

摘要: Zoledronic acid (ZOL) is an aminobisphosphonate able to inhibit the prenylation of intracellular proteins through inhibition farnesylpyrophosphate synthase. Prenylation essential for maintenance activation components signal transduction pathways regulating apoptosis and proliferation such as Ras Ras-related proteins. ZOL has demonstrated a direct anti-tumour effect in vitro preclinical models, its ability preventing skeletal-related events proven patients with bone metastases from different origins. Clinical evidence on anti-proliferative effects emerging. We describe several strategies order improve activity ZOL. In detail, we illustrate new combinations between cytotoxic drugs or other biological agents farnesyltransferase inhibitor tipifarnib focusing sequence administration these drugs. Moreover, efforts find molecular targets use technological platforms DNA microarrays are described.