Department of Medicine, University of Illinois at Chicago, 909 S. Wolcott, Chicago, IL 60612, USA.
Anticancer Res. 2013 Aug;33(8):2981-8.
Cancer patients suffer from cancer-induced bone pain, hypercalcemia, and reduced quality of life caused by pathological fractures. Many of these complications related to cancer can be treated, or at least controlled, using new anticancer agents. Recently, two agents used initially to treat osteoporosis demonstrated direct and indirect anticancer activity. In this review, we summarize current knowledge about direct and indirect anticancer activity of zoledronic acid (a third-generation bisphosphonate), and denosumab antibody against RANKL. Zoledronic acid influences the proliferation and viability of tumor cells in vitro, and effectively reduces tumor burden, tumor-induced pain, and tumor growth in vivo. Denosumab is a fully human monoclonal antibody preventing the binding of RANKL to its receptor on osteoclasts' membrane, and through this mechanism inhibits the resorption of the bone. Furthermore, this agent demonstrates direct anticancer activity through the RANKL signaling pathway. Because of these features both drugs may gain broader application for the treatment of cancer patients. However, further pre-clinical and clinical evaluation is needed for both agents to fully assess the antineoplastic mechanisms of activity of both agents.
癌症患者患有癌症引起的骨痛、高钙血症和病理性骨折导致的生活质量下降。许多与癌症相关的这些并发症可以通过使用新的抗癌药物来治疗，或者至少可以控制。最近，最初用于治疗骨质疏松症的两种药物表现出直接和间接的抗癌活性。在这篇综述中，我们总结了唑来膦酸（第三代双膦酸盐）和抗 RANKL 抗体地舒单抗的直接和间接抗癌活性的现有知识。唑来膦酸影响体外肿瘤细胞的增殖和活力，并有效地减轻肿瘤负担、肿瘤引起的疼痛和体内肿瘤生长。地舒单抗是人源化单克隆抗体，可防止 RANKL 与其在破骨细胞膜上的受体结合，并通过这种机制抑制骨吸收。此外，该药物还通过 RANKL 信号通路发挥直接的抗癌活性。由于这些特点，这两种药物可能会更广泛地应用于癌症患者的治疗。然而，这两种药物都需要进一步的临床前和临床评估，以充分评估两种药物的抗肿瘤活性的作用机制。
