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The bone\u2010derived factors fuel the vicious cycle by acting back on the tumor cells. The vicious cycle offers novel targets for the treatment of advanced cancers. Treatments can inhibit bone cells (osteoclasts and osteoblasts) that are stimulated by tumor\u2010secreted factors. Drugs can also inhibit tumor responses to factors enriched in the bone microenvironment, such as transforming growth factor\u2010\u03b2. Animal models show that these approaches, especially combination treatments, can reduce tumor burden. The results suggest a novel paradigm in which tumor growth can be effectively inhibited by drugs that target cells in the bone microenvironment and not the tumor cells themselves. J. Cell. 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