RANKL inhibition in the treatment of bone metastases.
RANKL inhibition in the treatment of bone metastases.
复制标题
DOI：
10.1097/spc.0b013e32830baac2
复制
发表时间：
2008-09-01
影响因子：
2.1
通讯作者：
Jun, Susie
中科院分区：
文献类型：
--
作者：
Lipton, Allan;Jun, Susie
审查目的：骨转移在晚期恶性肿瘤患者中很常见，并与肿瘤相关事件、癌症进展和死亡相关。核因子κ β受体激活因子配体（RANKL）及其受体RANK是破骨细胞分化和功能的关键介质，在转移性骨肿瘤引起的骨破坏中起关键作用。本文综述了RANKL对病理性骨疾病的贡献，并介绍了RANKL抑制人类转移性cancer.Recent发现的早期临床数据：RANKL/RANK相互作用是正常骨稳态所必需的。RANKL与RANK的结合诱导溶骨性骨吸收，这是一种当骨中存在肿瘤细胞时过量发生的过程。在癌症患者中，使用骨吸收标记物可测量的肿瘤诱导的骨质溶解增加可用于监测对治疗的反应或预测肿瘤进展。Denosumab是一种新型的、全人源的RANKL特异性单克隆抗体，可抑制多种转移性肿瘤患者的骨吸收标志物，目前正在多项临床试验中进行研究，用于预防和治疗骨转移瘤。正在进行临床试验，以评估地舒单抗治疗转移性癌症患者骨吸收的安全性和疗效。
PURPOSE OF REVIEW: Bone metastases are common in patients with advanced malignancies and are associated with skeletal-related events, cancer progression, and death. Receptor activator of nuclear factor kappa beta ligand (RANKL) and its receptor, RANK, key mediators of osteoclast differentiation and function, play a pivotal role in bone destruction induced by metastatic bone tumors. The present review summarizes the contribution of RANKL to pathologic bone disease and presents early clinical data on RANKL inhibition in human metastatic cancer.RECENT FINDINGS: RANKL/RANK interactions are essential for normal bone homeostasis. Binding of RANKL to RANK induces osteolytic bone resorption, a process that occurs in excess when tumor cells are present in bone. In cancer patients, increased tumor-induced osteolysis that is measurable using bone resorption markers can be used to monitor response to treatment or predict tumor progression. Denosumab, a novel, fully human monoclonal antibody specific to RANKL, suppresses bone resorption markers in patients with a variety of metastatic tumors and is being investigated in multiple clinical trials for the prevention and treatment of bone metastases.SUMMARY: RANKL is an appropriate target to reduce the osteolytic bone damage caused by bone metastases. Clinical trials are ongoing to assess the safety and efficacy of denosumab for the treatment of bone resorption in patients with metastatic cancers.