Zoledronic Acid Zings Cervical Cancer

Cervical cancer is the second most common cancer among women worldwide. Research has shown that progression of the pre-malignant stages to invasive cervical cancer is associated with the onset of new blood vessel growth called angiogenesis. Using a mouse model of cervical cancer to explore the molecular control of angiogenesis in cancer progression, Douglas Hanahan and colleagues, from the University of California, San Francisco, found that a drug called zoledronic acid was able to halt the progression of cervical cancer in these mice. The researchers first showed that cervical cancers in this mouse model had several characteristics similar to human cervical cancer. They further found that an important player in cervical cancer progression was an enzyme called matrix metalloprotease-9, which stimulated angiogenesis. The researchers treated these mice with bisphosphonate, zoledronic acid, a matrix metalloprotease inhibitor that is already FDA-approved for treatment of patients with bone metastases. Zoledronic acid treatment in the mouse model impaired angiogenesis and slowed cervical tumor progression and growth. The researchers showed that this drug acted by both decreasing matrix metalloprotease-9 gene expression and inhibiting the activity of any remaining matrix metalloprotease-9 protein. This study provides evidence that an already approved drug, zoledronic acid, may be useful for therapy in cervical cancer and other diseases resultant from matrix metalloprotease-9 expression and activity.

TITLE: An amino-bisphosphonate targets MMP-9expressing macrophages and angiogenesis to impair cervical carcinogenesis

AUTHOR CONTACT:
Douglas Hanahan
University of California, San Francisco, 513 Parnassus Avenue San Francisco, CA 94143, USA
Phone: 415-476-9209; Fax: 415-731-3612; E-mail: dh@biochem.ucsf.edu

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Contact: Laurie Goodman
press_releases@the-jci.org
212-342-4159
Journal of Clinical Investigation
1-Sep-2004