Potentials for RNAi in sarcoma research and therapy: Ewing's sarcoma as a model

Potentials for RNAi in sarcoma research and therapy: Ewing's sarcoma as a model
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DOI:
10.1016/s1044-579x(03)00041-5
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发表时间:
2003-08-01
影响因子:
14.5
通讯作者:
Pospisilova, S
Pospisilova, S
中科院分区:
医学1区
文献类型:
--
作者:
Kovar, H;Ban, J;Pospisilova, S

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现有的数据表明EWS-FLI 1是持续尤文肉瘤生长不可或缺的,也是这种疾病的理想治疗靶点。siRNA可能作为融合基因特异性试剂具有很大的前景。RNAi介导的EWS-FLI 1抑制可能导致肿瘤细胞表型改变,包括化学敏感性的变化和恢复的分化潜力。因此,RNAi可以作为化疗的辅助。然而,作为一种治疗手段,RNAi受到药剂递送的限制和抗性克隆的出现的阻碍。EWS-FLI 1表达的体外抑制将允许定义可能引起晚期复发的休眠肿瘤细胞的表型特征,从而能够改善诊断和治疗,甚至是最小残留疾病。(C)2003爱思唯尔有限公司。保留所有权利。
Existing data identify EWS-FLI1 as indispensable for sustained Ewing's sarcoma growth and as the ideal therapeutic target in this disease. The siRNA may hold great promises as a fusion gene specific agent. RNAi mediated suppression of EWS-FLI1 is likely to result in an altered tumor cell phenotype including changes in chemosensitivity, and a restored differentiation potential. Thus, RNAi may serve as an adjuvant to chemotherapy. As a therapeutic means however, RNAi is hampered by limitations in the delivery of the agent and emergence of resistant clones. In vitro suppression of EWS-FLI1 expression will allow to define the phenotypic characteristics of dormant tumor cells that may give rise to late relapses, enabling improved diagnosis and treatment even of minimal residual disease. (C) 2003 Elsevier Ltd. All rights reserved.