A Step in the Journey of Denosumab From Bone-Targeted Therapy to Seed- and Soil-Targeted Therapy

Oral or intravenous bisphosphonates are largely used in on-cology and can be considered as bone-targeted therapies. Deno-sumab represents a new therapeutic opportunity by targeting the receptor activator of nuclear factor B ligand (RANKL) system, which has been has been linked to osteoclast formation, activity, and survival.1,2 Clinical activity of this compound on bone density in the setting of adjuvant aromatase inhibitor therapy for early breast cancer has recently been reported in Journal of Clinical Oncology.3 In this issue, Fizazi et al4 present another aspect of denosumab development through a randomized phase II study of 111 patients with bone metastases or myeloma, evaluating two schedules of denosumab compared with placebo. In this study, tumor types weremainly prostate or breast cancer (45%and 41%, respectively); 8 % of patients had myeloma. Denosumab activity has been re