The role of RANK-ligand inhibition in cancer: the story of denosumab.
The role of RANK-ligand inhibition in cancer: the story of denosumab.
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DOI：
10.1634/theoncologist.2010-0154
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Cortes-Funes H
中科院分区：
文献类型：
--
作者：
Castellano D;Sepulveda JM;García-Escobar I;Rodriguez-Antolín A;Sundlöv A;Cortes-Funes H
骨是晚期癌症患者中非常常见的转移部位。骨骼转移在乳腺癌和前列腺癌中最常见，但几乎任何晚期癌症都可能扩散到骨骼。基于对骨重建过程的最新了解，开发了Denosumab（一种抗RANK-L的全人源单克隆抗体）。III期临床试验证明，地舒单抗在治疗骨转移患者的骨丢失和预防肿瘤相关事件方面耐受性良好且有效。骨转移的诊断是对患者具有一定后果的事件。它们通常意味着疼痛，也可能意味着病理性骨折、高钙血症和脊髓压迫，所有这些都意味着生活质量下降，通常也意味着住院治疗。自从静脉注射双磷酸盐药物出现后，骨质疏松患者的情况开始好转，骨破坏的时间延长了。下一代骨转移治疗药物正处于临床开发阶段，其中最先进的药物是狄诺塞单抗。Denosumab是一种全人源单克隆抗体，通过与核因子κ B配体的受体活化剂结合，抑制破骨细胞成熟、活化和功能，最终结果是降低骨吸收率。在这篇综述中，我们概述了狄诺塞单抗在一般实体瘤患者和特别是前列腺癌患者中使用的相关临床前和临床数据。
The bone is a very common site of metastasis in patients with advanced cancer. Skeletal metastases are most common in breast and prostate cancer, but virtually any advanced cancer may disseminate to the bone. On the basis of recent advances in the understanding of bone remodeling processes, denosumab, a fully human monoclonal antibody against RANK-L, has been developed. Phase III clinical trials have demonstrated that denosumab is well tolerated and effective in the treatment of bone loss and prevention of skeletal-related events in patients with bone metastases. The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases—bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.
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20.3
作者：
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