NEW YORK (Reuters Health) - In a mouse model of human cervical cancer, treatment with the bisphosphonate zoledronic acid impairs cervical carcinogenesis by targeting a pro-angiogenic protease implicated in mobilizing VEGF (vascular endothelial growth factor). Zoledronic acid is approved in the U.S. for the treatment of bone metastases from solid tumors and for hypercalcemia of malignancy.
Reporting the findings in the September issue of the Journal of Clinical Investigation, researchers from the University of California, San Francisco say zoledronic acid “holds promise” for antiangiogenic therapy of cervical cancer as well as other cancers and diseases involving metalloprotease-9 (MMP-9).
In their studies, zoledronic acid (Zometa; Novartis) inhibited angiogenesis in both premalignant cervical intraepithelial neoplasia (CIN-3) and in malignant cervical tumors. “Therapeutic regimens using zoledronic impaired progression from premalignant lesions to invasive carcinoma and antagonized the growth of preexisting cervical tumors,” Dr. Douglas Hanahan and colleagues report.
Zoledronic acid, they’ve found, works by decreasing both macrophage expression and proteolytic activity of MMP-9, “reducing association of VEGF with its receptor on angiogenic endothelial cells.”
The findings “are likely to be relevant to human cervical carcinogenesis,” the team notes, as MMP-9 is upregulated in CIN-3 lesions and cervical cancers in humans and “elevated expression and activity correlate with poor prognosis for subsequent metastasis and tumor recurrence.”
Based on zoledronic acid’s ability to inhibit premalignant lesions and given its track record of safety, they suggest in their report that the drug might have a role as adjuvant therapy following excision of CIN-3 lesions in women at high risk for recurrence and progression.
Also, with its ability to interfere with established cervical cancers, “perhaps zoledronic acid could be added to the standard of care for cervical cancer to assess its potential for improving efficacy by inhibiting angiogenesis.” Clearly, more study is needed, Dr. Hanahan and colleagues conclude.
Source: J Clin Invest 2004;114:623-633. [ Google search on this article ]
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