RANK Ligand: Effects of Inhibition
RANK Ligand: Effects of Inhibition
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DOI：
10.1007/s11912-010-0088-1
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发表时间：
2010-03-01
影响因子：
4.7
通讯作者：
Bukowski, Ronald M.
中科院分区：
文献类型：
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作者：
George, Saby;Brenner, Andrew;Bukowski, Ronald M.
活化B细胞核因子κ轻链增强子受体激活剂（RANK）及其配体（RANKL）属于肿瘤坏死因子（TNF）超家族。RANK mRNA在骨和骨髓中广泛表达。它在刺激破骨细胞分化和成熟以及防止细胞凋亡方面具有重要作用。因为破骨细胞活性是恶性肿瘤中骨吸收的一个重要方面，所以靶向这些细胞是预防恶性肿瘤中骨相关事件的一个很好的理由。临床前研究已证明Denosumab在预防小鼠骨丢失和改善骨密度方面的疗效。狄诺塞单抗是一种抗RANKL的全人源单克隆抗体，已证明其可有效降低RANK信号传导，从而降低破骨细胞活性。它已在大型，随机，3期研究中被证明可有效预防骨折和骨丢失，并在各种癌症和非癌症环境中改善骨密度。本文综述了RANKL抑制的最新证据及其临床意义。
Receptor activator of nuclear factor kappa-light-chain-enhancer of activated B-cells (RANK) and its ligand (RANKL) belong to the tumor necrosis factor (TNF) superfamily. RANK mRNA is expressed widely in bone and bone marrow. It has a significant role in stimulating osteoclast differentiation and maturation, and also in preventing apoptosis. Because osteoclast activity is an important aspect of bone resorption in malignancy, targeting these cells is a good rationale for preventing skeletal-related events in malignancies. Preclinical studies have demonstrated the efficacy of denosumab in preventing bone loss in mice and improving bone mineral density. Denosumab is a fully human monoclonal antibody against RANKL, which has been shown to be effective in reducing signaling via RANK and thus osteoclast activity. It has been demonstrated in large, randomized, phase 3 studies to be effective in preventing fractures and bone loss, and improving the bone mineral density in various cancerous and noncancerous settings. This article reviews the latest evidence of RANKL inhibition and its clinical implications.