Abstract
Objectives Zoledronic acid may have potential antitumor activity; it is the most active agent among the bisphosphonates in blocking the prenylation (activation) of small signaling proteins required for cell function and survival. This presentation discusses the results of preclinical studies evaluating the antitumor activity of zoledronic acid and discusses initiated clinical studies. Methods Experimental models included nude mice bearing human prostate cancer cells, castrated rats, and in vitro endothelial cells. Results Zoledronic acid inhibited osteolytic and osteoblastic bone lesions in mice bearing human prostate cancer cells. Zoledronic acid also inhibited endothelial cell proliferation and capillary-like tube formation in vitro and testosterone-induced revascularization of the prostate in castrated rats without altering testosterone activity directly. The ZEUS study is one of several studies investigating whether zoledronic acid may prevent bone metastases. Conclusions The preclinical data on the antitumor effects of zoledronic acid were encouraging. Therefore, the role of zoledronic acid in earlier-stage prostate cancer is being investigated in clinical trials. The results of these trials are awaited to evaluate the effects in patients with prostate cancer.
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