Development of new therapies for the treatment of bone metastases

Breast cancer frequently metastasizes to the skeleton causing bone destruction. We have shown that Halofuginone (Hfg), a plant alkaloid derivate, 1) reduces osteolytic bone metastasis through inhibition of TGF-beta and BMP signaling; and 2) induces bone loss by increasing bone resorption and decreasing bone formation. To further evaluate the mechanism for Hfg-induced bone loss, we tested a combined treatement of Hfg with zoledronic acid (ZOL) to determine if we could prevent Hfg-induced bone loss in normal mice and the combination therapy could be beneficial in our model of breast cancer bone metastases using MDA-MB-231 cells. Our results showed that Hfg reduced breast cancer bone metastases and this effect is enhanced with Hfg-ZOL combined therapy. Further, ZOL prevented Hfg-induced bone loss in mice. Hfg has completed Phase II trials for use in sarcoma and could rapidly be brought to the clinic for the treatment of patients with breast cancer bone metastases.