Preclinical Profile of Zoledronic Acid in Prostate Cancer Models

Abstract

Objective: To describe the preclinical data from animal models of prostate cancer demonstrating the pharmacologic effects of zoledronic acid on bone metabolism and tumor growth. Methods: Published data were reviewed. Results: In animal models, zoledronic acid has been shown to decrease tumor-induced osteolysis, prevent bone metastasis, and reduce skeletal tumor burden. In androgen-deficient mice injected intracardially with PC-3 human prostate cancer cells, zoledronic acid reduced bone metastases. In a model of prostate tumors growing in the tibiae of mice, zoledronic acid significantly inhibited growth of both osteolytic and osteoblastic tumors and reduced circulating levels of prostate-specific antigen. Data from preclinical studies demonstrate that zoledronic acid has effects not only on osteoclasts, but also on osteoblasts and tumor cells. Zoledronic acid can disrupt the interactions between tumor cells and the bone microenvironment that promote tumor growth in the bone. Zoledronic acid has also been shown to inhibit proliferation and induce apoptosis of human prostate cancer cell lines in vitro and has enhanced antitumor activity when combined with taxanes. In addition, zoledronic acid appears to inhibit tumor cell invasion of the extracellular matrix and angiogenesis. Conclusions: Zoledronic acid has potent antitumor effects in prostate cancer models of bone metastases. Further preclinical studies are needed to fully elucidate the biochemical mechanisms responsible for this activity.