RANKL inhibition is an effective adjuvant for docetaxel in a prostate cancer bone metastases model
RANKL inhibition is an effective adjuvant for docetaxel in a prostate cancer bone metastases model
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DOI：
10.1002/pros.20744
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发表时间：
2008-06-01
期刊：
影响因子：
2.8
通讯作者：
Keller, E. T.
中科院分区：
文献类型：
--
作者：
Ignatoski, K. M. Woods;Escara-Wilke, J. F.;Keller, E. T.
背景多西他赛在晚期前列腺癌（PCa）男性中诱导抗肿瘤反应;然而，多西他赛治疗相关的副作用可能很严重，导致治疗中止。因此，需要确定一种有效的辅助治疗，以允许更低剂量的多西他赛。晚期PCa通常伴有骨转移。NF κ B受体激活因子配体（RANKL）是一种关键的促骨形成因子。靶向RANKL降低小鼠模型中骨中PCa生长的建立和进展。在小鼠胫骨内模型中，检测了使用与免疫球蛋白Fc结构域融合的重组可溶性RANK胞外结构域（RANK-Fc）抑制RANKL作为多西他赛辅助治疗pCa骨转移的疗效。RANK-Fc和多西他赛联合用药降低骨肿瘤负荷的作用大于单独使用。多西他赛联合RANKL抑制剂治疗晚期PCa值得进一步研究。
BACKGROUND. Docetaxel induces an anti-tumor response in men with advanced prostate cancer (PCa); however, the side effects associated with docetaxel treatment can be severe, resulting in discontinuation of therapy. Thus, identification of an effective adjuvant therapy to allow lower doses of docetaxel is needed. Advanced PCa is typically accompanied by skeletal metastasis. Receptor activator of NFkB ligand (RANKL) is a key pro-osteoclastic factor. Targeting RANKL decreases establishment and progression of PCa growth in bone in murine models.METHODS. The efficacy of inhibiting RANKL, using a recombinant soluble RANK extracellular domain fused with the immunoglobulin Fc domain (RANK-Fc), was tested as an adjuvant therapy with docetaxel for pCa bone metastasis in a murine intra-tibial model.RESULT. The combination of RANK-Fc and docetaxel reduced tumor burden in bone greater than either treatment alone.CONCLUSION. The combination of docetaxel with a RANKL-inhibiting agent merits further investigation for treatment of advance PCa.