The bisphosphonate zoledronic acid has been reported to produce antitumor effects, although the mechanisms of such effects remain unclear. In a study reported in Clinical Cancer Research, Gonzalez-Villasana and colleagues found evidence that zoledronic acid inhibited ovarian cancer angiogenesis by inhibiting Rac1 activation.
In in vitro studies, zoledronic acid inhibited ovarian cancer cell invasion with HeyA8-MDR and OVCAR-5 cell lines, reduced production of proangiogenic cytokines, inactivated Rac1, and decreased the levels of Pak1/p38/matrix metalloproteinase 2.
In mouse models, zoledronic acid treatment reduced tumor growth, angiogenesis, and cell proliferation and inactivated Rac1 in both HeyA8-MDR and OVCAR-5 models. The antitumor effects were increased in both mouse models when zoledronic acid was combined with nab-paclitaxel (Abraxane).
The investigators concluded: “[Zoledronic acid] has robust antitumor and antiangiogenic activity and merits further clinical development as [ovarian cancer] treatment.” ■
Gonzalez-Villasana V, et al: Clin Cancer Res. January 16, 2015 (early release online).