The estrogen metabolite 2-methoxyestradiol (2ME₂) has emerged as a promising anticancer agent due to its potent growth-inhibitory and proapoptotic effects on tumor cells. In this issue, Cicek and colleagues demonstrate that 2ME₂ inhibits tumor growth in bone marrow and soft tissues, tumor cell metastasis to bone, and tumor-induced osteolysis in vivo in a mouse model of estrogen receptor–negative metastatic breast cancer. Furthermore, the authors document that 2ME₂ induces apoptosis of mononuclear TRAP-positive cells and multinucleated osteoclasts, revealing a mechanism by which 2ME₂ reduces tumor-induced osteolysis. These findings concluded that the ability of 2ME₂ to target tumor growth, metastasis to bone, and osteolysis are of considerable clinical significance. These exciting data support a novel therapeutic approach to treatment of advanced breast cancer. For details, see the article by Cicek and colleagues on page 10106 of this issue.

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