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Combination therapy of **denosumab** (a fully human monoclonal antibody targeting RANK ligand) with **standard chemotherapy** refers to a regimen where denosumab’s inhibition of RANKL-mediated osteoclast activation is paired with cytotoxic agents commonly used as standard therapies for cancer (e.g., cisplatin, doxorubicin, or other conventional chemotherapeutics, depending on diagnosis). Denosumab’s main mechanism is to reduce bone resorption and prevent skeletal-related events in malignancies with bone involvement. The efficacy and safety of this combination remain experimental, with some studies reporting no meaningful clinical benefit over chemotherapy alone, and, in certain contexts (such as osteosarcoma), potential antagonistic interaction with chemotherapy efficacy has been suggested. Denosumab is developed by Amgen, and chemotherapies included may be manufactured by various companies. The combination is not FDA approved as a fixed regimen for any indication. Clinical trials have studied or are studying this regimen in cancers such as non-small cell lung cancer, osteosarcoma, and metastatic peripheral nerve sheath tumor.
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