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Effect of radium-223 on breast cancer bone metastases in mice



DOI:10.1038/bonekey.2013.191

In this pre-clinical study, Suominen et al. looked at the effect of radium-223 dichloride (radium-223) on cell cultures (osteoclasts, osteoblasts and breast cancer cells) and in a mouse model of breast cancer bone metastasis, either alone or in combination with zoledronic acid or doxorubicin.

In vitro, radium-223 inhibited breast cancer cell proliferation and prevented differentiation of osteoclasts and osteoblasts. Mice treated with a single dose of radium-223 were significantly less likely to develop cancer-induced cachexia; none of the 14 treated mice developed cachexia compared with 7 of 14 control mice. The treated animals also showed decreased osteolysis (56% vs controls) and reduced tumor growth (43% vs controls). The maximum survival, observed in the group of mice treated with radium-223 in combination with doxorubicin, was 31.5 days, vs 29.2 days in controls (P<0.01).

Editor’s comment: This study supports the case for clinical development of radium-223 for treating metastatic hormone-refractory breast cancer. It also provides insights into the mechanisms of action of radium-223, pinpointing osteoblasts as one of the cellular targets of this calcium mimetic. Interestingly, prostate cancer bone metastases are mainly osteoblastic lesions. This may help explain the efficacy of radium-223 in the ALSYMPCA clinical trial – osteoblasts must take up a large amount of radium-223. Experimental data suggest that radium-223 is also active in osteoclasts, so it will be interesting to determine whether radium-223 has similar efficacy in metastatic patients with osteolytic lesions.


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