Genetic profiling of tumors has revealed important regulators of the metastatic process and suggested novel targets for cancer therapeutics. Targeting the tumor cell alone is not sufficient; multimodality therapy against tumor cells, their growth factors and the essential accessory cells with which cancer cells interact is imperative. In the bone marrow and within the tumor stroma, two niches constitute highly specific, physiologically defined sites; the vascular and stromal niche. A high preponderance of tumor cells is found in the bone marrow of patients with malignancy, even in the absence of overt distant metastases. Bisphosphonates inhibit normal and pathologic osteoclast-mediated bone resorption. Denosumab inhibits the maturation of osteoclasts by binding to RANKL, protecting the bone from degradation.
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